Chemotherapeutic drugs, particularly alkylating cytotoxics such as cyclophosphamide (CYP) play a ... more Chemotherapeutic drugs, particularly alkylating cytotoxics such as cyclophosphamide (CYP) play a great job in inducing premature ovarian failure (POF). Hormone replacement therapy (HRT) is a widely used medication to improve hormone secretion. However, long-term HRT increases the risk of breast cancer and cardiovascular disease is concerning. Therefore, there is an urgent need to develop a safe and effective treatment for POF. Bone Marrow-(BM-MSCs) and Umbilical Cord-(UC-MSCs) derived stem cells (SCs) were isolated and identified from healthy rats. For POF induction, CYP (200mg/Kg b.wt) injected (i.p) into CYP, CYP+BMSCs, and CYP+UCMSCs followed by another dose (10mg/ b.wt, i.p) after one week. The normal control (NC) group were injected with saline. After two weeks of POF induction MSCs (1 × 10 6 cells/ml) of media were transplanted into POF rats through tail-vein. The effects of MSCs transplantation to POF were evaluated through sex hormones, iron, and complete blood count (CBC) analysis. POF-induced rats showed a significant increase in serum FSH and LH, with marked decrease in anti-Mullerian hormone (AMH) and estradiol (E2). Obvious increase in serum iron level observed in CYP group compared to the NC. Moreover, POF-induced rats displayed leucopenia, erythrocytopenia, and thrombocytopenia with a significant reduction in Hb, PCV, MCV, MCH, and MCHC compared to the NC. Administration of MSCs to CYPinjured rats significantly improved female reproductive hormones disturbances, iron, and hemogram. It was suggested that MSCs was a potential approach for improving sex hormones, iron, and hematological alterations, and potentially promoting the restoration of CYP-induced POF.
Premature ovarian failure (POF) contributes significantly to female infertility in young women. I... more Premature ovarian failure (POF) contributes significantly to female infertility in young women. It mainly developed after chemotherapy medication, particularly with alkylating cytotoxic such as cyclophosphamide (CYP). The present study was designed to determine the advantages of mesenchymal stem cells (MSCs) as therapy for POF conditions in female rat models. For POF induction, CYP (200mg/Kg b.wt) was injected intraperitoneally (i.p) followed by another activation dose of CYP (10mg/ b.wt, i.p) after one week. MSCs treatment was enhanced by Bone Marrow-derived stem cells (BM-MSCs) or Umbilical Cord-derived stem cells (UC-MSCs) after two weeks of POF induction. The normal control (NC) group rats were injected with saline. The effects of POF modeling and MSCs (1 × 10 6 cells) transplantation through tail-vein were examined by sex hormonal analysis and morphological examination of ovarian follicles. CYP-induced rats POF showed a significant reduction in AMH and E2 concentrations in addition to total, primordial, primary, secondary, and mature graffian follicles in contrast to the NC group (P<0.0001). The FSH and LH concentrations were increased in the CYP group and degenerated follicles than in the NC group (P<0.0001). Transplanting MSCs improved the histopathological and hormonal analysis of the ovarian microenvironment induced by CYP (P<0.0001) with no significant difference in response to BM-MSCs or UC-MSCs. It was concluded that MSCs injection was a possible strategy for improving CYP-induced morphological changes, and sex-hormonal alterations, potentially promoting the restoration of CYP-induced infertility via POF.
A potential therapeutic impact of Gallic acid in a rat model of hepatocarcinogenesis through inhi... more A potential therapeutic impact of Gallic acid in a rat model of hepatocarcinogenesis through inhibition of cell proliferation and oncogenic miRNA-221 and induction of apoptosis by Nrf-2 /Bcl-2/TGF-β1 signaling pathways.
Hepatocellular carcinoma (HCC) accounting about 75% of hepatic neoplasia, making it the most comm... more Hepatocellular carcinoma (HCC) accounting about 75% of hepatic neoplasia, making it the most common kind of liver cancer worldwide. So, this study was planned to evaluate the beneficial chemopreventive efficacy of hesperidin (Hes) in experimental model of Diethyl nitrosamine (DEN) / Carbon tetrachloride (CCl 4)-induced HCC in rats. Thirty male rats were divided into 3 equal groups. Group 1 (normal control): rats didn't receive any treatment. Group 2 (HCC): HCC was induced in rats by injection of DEN (200mg/kg b.w/i.p), then 2 weeks later of DEN injection rats received 3 weekly successive doses of CCl 4 (3ml/kg b.wt/ orally) at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl 4 administration were repeated once again after 5 weeks. Group 3 (HCC+ hesperidin): 15 weeks after HCC induction, rats treated with Hes (150 mg/kg b.wt), orally and continued for 6 weeks. A significant increase in serum ALT, AST and ALP activities were observed in HCC-induced rats. However, significant downregulation of liver Nrf2, Caspase-3, Bcl-2 and MicroRNA-34a with upregulation of FGF-2 and MicroRNA-221 with Global DNA hyper-methylation were observed in HCC group. Hesperidin treatment exhibited downregulation of microRNA-221 and FGF-2 with upregulation of Nrf2, Bcl-2, caspase 3 gene and Global DNA hypo-methylation. Interestingly, improvement of liver histopathological alterations supported the chemopreventive activity of Hesperidin. Conclusively, Hesperidin ameliorates the progression of HCC and has promising chemopreventive, and antiangiogenic activity, inhibiting growth promoting oncogene and initiation of gene regulating apoptosis and protects the liver from oxidative damage and inflammation.
The antioxidative, anti-inflammatory, anticancer, and hepatoprotective qualities of ginger have b... more The antioxidative, anti-inflammatory, anticancer, and hepatoprotective qualities of ginger have been well-established. This research was purposed to evaluate both ginger extract (GE) and ginger nanoparticles (GNPs) potential chemotherapeutic influences in mitigating hepatocellular carcinoma (HCC) induced by carbon tetrachloride (CCl4) and diethylnitrosamine (DEN) in rats. HCC was induced in rats through DEN injection (200 mg/kg b.w./I.P.). Subsequently, after a two-week interval, rats were exposed to three consecutive weekly doses of CCL4 (3 mL/kg b.w. orally), prepared in a 1:1 dilution with corn oil, serving as a carcinogenic promoter. CCL4 and DEN administration were repeated following an additional 5-week interval. Fifteen weeks after HCC induction, oral treatment with GE (300 mg/kg b.w./day) and GNPs (50 mg/kg b.w./day) was initiated and continued for 6 weeks. Twenty-eight rats were divided evenly into four subgroups: G1 (normal control), G2 (DEN/CCL4 induced HCC), G3 (DEN/CCL4+GE), and G4 (DEN/CCL4+GNPs). The results demonstrated a substantial elevation in AST, ALT, and ALP serum activities and a decrease in liver microRNA-29 expression in rats with induced hepatocellular carcinoma. High levels of TGF-β1, FGF, and HGF also pointed to upregulation during the development of HCC. Treatment with GE and GNPs led to a significant reduction in liver marker enzymes and the heightened expression of TGF-β1, FGF2, and HGF, accompanied by an upregulation of microRNA-29 in rats with liver cancer. In conclusion, GE and GNP treatments may serve as chemotherapeutic agents by activating the tumor suppressor microRNA-29 gene and suppressing angiogenesis growth factors in the liver.
Hepatocellular carcinoma (HCC) is the second most fatal cancer, caused by either factors outside ... more Hepatocellular carcinoma (HCC) is the second most fatal cancer, caused by either factors outside the body or even with hereditary or genetic changes. The potential chemotherapeutic effect of ginger extract (GE) and ginger nanoparticles (GNPs) against diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) induced HCC in rats was evaluated. HCC was induced via utilizing DEN injection (200 mg/kg b. wt/ I.P), then 2 weeks later of DEN injection rats received 3 weekly successive doses of CCl4 diluted with corn oil at a ratio of 1:1(3ml/kg b.wt) orally to boost the carcinogenic impact. The administration of DEN and CCl4 was repeated after a period of 5 weeks. 15 weeks after HCC induction, treatment with GE (300mg/kg b.wt/day) and GNPs (50mg/kg b.wt/day) were given orally and continued for six weeks. Twenty-four male rats were separated into four equal groups. Group 1 (normal control): Rats received saline as a vehicle, Group 2: (DEN/CCl4 induced HCC), Group 3: (DEN/CCl4 +GE), and Group 4: (DEN/CCl4 +GNPs). The results revealed significant upregulation in liver microRNA-221 with obvious down-regulation of Nrf2 and Bcl-2 and insignificant downregulation in caspase 3 gene in HCC-induced rats. GE and GNPs treatment exhibited a significant decrease in liver marker enzymes with downregulation of microRNA-221 and upregulation of Nrf2, Bcl-2 and caspase 3 gene expression. These findings suggested that GE and GNPs have a beneficial therapeutic effect against liver cancer, inhibiting growthpromoting oncogene and increasing apoptosis.
The Hepatitis C virus causes acute and chronic hepatitis. Micro RNA could be used as disease biom... more The Hepatitis C virus causes acute and chronic hepatitis. Micro RNA could be used as disease biomarkers. This study looked into Micro RNA125b, Micro RNA 489-3p, and biochemical analysis as a diagnostic for HCV. This study included 20 individuals who had chronic liver disease and were admitted to the Gastroenterology Hospital in Mansoura and the Oncology Institute in Mansoura. All individuals were subjected to full clinical examinations. Following analysis of all patients, polymerase chain reaction (PCR) was confirmed to be positive for chronic HCV in 5 individuals. Five negative control samples were taken from a healthy control group of the same age range and sex. Serum liver function parameters and AFP with gene expression of microRNA125b and microRNA 489-3p were estimated. The HCV group significantly increased AST, ALT, DBIL, TBIL, ALP, GGT, and ALB) while significantly decreasing albumin concentrations. In the HCV group, AFP was substantially higher than in control. The HCV group had a considerable rise in miRNA125b (10.07+ 0.19) but a significant drop in miRNA489-3p (0.36+ 0.02). In addition to biochemical investigation, we found that miRNA125b and miRNA489-3p expression levels were employed as valuable markers for HCV diagnosis.
Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is ... more Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is the frequent reason for cirrhosis all over the world. MicroRNA could be used as a disease biomarker. This investigation was carried out to investigate mRNA-125b, mRNA 489-3p, and biochemical analysis as markers for chronic HBV. This work included 20 patients who had chronic liver disease admitted to the Gastroenterology Hospital and Oncology Institute in Mansoura. After investigation, serum samples were obtained from five patients that were positive for PCR chronic HBV. For control, negative serum samples were collected at the same age range and sex. Liver function and alpha fetoprotein (AFP) parameters were estimated. RNA was extracted from serum for gene expression of mRNA125b and mRNA 489-3p. The main results showed that the HBV group had a significant increase in ALT, AST, TBIL, GGT, ALP, and AFP, while there was a significant decrease in albumin levels compared to the control group. HBV group showed a significant increase (6.70 ± 0.18) in mRNA125b, but a significant decrease in mRNA489-3 (0.51±0.03). In conclusion, mRNA125b and mRNA489-3p expressions along with biochemical analysis could be used as accurate markers for HBV diagnosis. HBV MicroRNA 125b MicroRNA 489-3p
Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is ... more Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is the frequent reason for cirrhosis all over the world. MicroRNA could be used as a disease biomarker. This investigation was carried out to investigate mRNA-125b, mRNA 489-3p, and biochemical analysis as markers for chronic HBV. This work included 20 patients who had chronic liver disease admitted to the Gastroenterology Hospital and Oncology Institute in Mansoura. After investigation, serum samples were obtained from five patients that were positive for PCR chronic HBV. For control, negative serum samples were collected at the same age range and sex. Liver function and alpha fetoprotein (AFP) parameters were estimated. RNA was extracted from serum for gene expression of mRNA125b and mRNA 489-3p. The main results showed that the HBV group had a significant increase in ALT, AST, TBIL, GGT, ALP, and AFP, while there was a significant decrease in albumin levels compared to the control group. HBV group showed a significant increase (6.70 ± 0.18) in mRNA125b, but a significant decrease in mRNA489-3 (0.51±0.03). In conclusion, mRNA125b and mRNA489-3p expressions along with biochemical analysis could be used as accurate markers for HBV diagnosis. HBV MicroRNA 125b MicroRNA 489-3p
Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species... more Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species (ROS) scavenger and good metal chelator, rich in phenolic hydroxyl groups that have strong antioxidant activity. For the present study, the strong antioxidant activity of QUR on several biochemical parameters in blood and liver of male rats exposed to high fat diet (HFD) induced non alcoholic steatohepatitis (NASH), were investigated. Sixty white male albino rats weighting 150-200 gm were used in this study. The rats were divided into four equal groups. 1) Normal group: received no drugs. 2) NASH group: received HFD daily for 12 weeks. 3) NASH + Quercetin group: received HFD daily for 3 months then QUR treatment (50 mg/kg body weight) through intraperitoneal route (i.p) daily for 10 weeks after induction of NASH. Blood and liver samples were collected from all animal groups two times, after the 6 th and 10 th week of treatment period. Serum was separated for determination of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). The obtained results revealed that, HFD supplementation exhibited a significant increase in: 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. QUR administration in NASH rats exhibited a significant increase in all mentioned parameters. On contrast, HFD supplementation exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed. QUR administration in NASH rats exhibited significant increase in all mentioned parameters. From the obtained results, it could be concluded that, the potential of QUR as natural antioxidant act as a powerful agent against the harmful effects of NASH.
Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species... more Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species (ROS) scavenger and good metal chelator, rich in phenolic hydroxyl groups that have strong antioxidant activity. For the present study, the strong antioxidant activity of QUR on several biochemical parameters in blood and liver of male rats exposed to high fat diet (HFD) induced non alcoholic steatohepatitis (NASH), were investigated. Sixty white male albino rats weighting 150-200 gm were used in this study. The rats were divided into four equal groups. 1) Normal group: received no drugs. 2) NASH group: received HFD daily for 12 weeks. 3) NASH + Quercetin group: received HFD daily for 3 months then QUR treatment (50 mg/kg body weight) through intraperitoneal route (i.p) daily for 10 weeks after induction of NASH. Blood and liver samples were collected from all animal groups two times, after the 6 th and 10 th week of treatment period. Serum was separated for determination of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). The obtained results revealed that, HFD supplementation exhibited a significant increase in: 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. QUR administration in NASH rats exhibited a significant increase in all mentioned parameters. On contrast, HFD supplementation exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed. QUR administration in NASH rats exhibited significant increase in all mentioned parameters. From the obtained results, it could be concluded that, the potential of QUR as natural antioxidant act as a powerful agent against the harmful effects of NASH.
Non alcoholic steatohepatitis (NASH) is a pathological condition characterized by accumulation of... more Non alcoholic steatohepatitis (NASH) is a pathological condition characterized by accumulation of lipids in the liver of non alcoholic individuals and consequent oxidative stress leading to cirrhosis of liver in the long run. Silymarin is a unique flavonoid complex extract isolated from seeds of the milk thistle plant (Silybum marianum) and has strong antioxidant and radical scavenging properties. The present research aimed to evaluate the therapeutic effects of silymarin (Slym) as natural antioxidant and anti-inflammatory on liver tissue of male rats exposed to experimental model of non alcoholic steatohepatitis (NASH) induced by supplementation of high fat diet (HFD) for 3 months, Through evaluation of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). HFD supplementation induced a significant increase in 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. On contrast, it exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed after HFD supplementation. Silymarin treatment was able to mitigate and ameliorate hepatic NASH induced by HFD and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status and antioxidant enzymes toward control levels. Silymarin treatment was highly effective against HFD induced NASH. The results of the present study suggest that silymarin has the potential to exert curative effects against liver NASH.
The present research aimed to evaluate the hepato/neuroprotective effects of Rutin and Resveratro... more The present research aimed to evaluate the hepato/neuroprotective effects of Rutin and Resveratrol as natural antioxidants on brain and liver tissues of experimental rats exposed to acute liver failure induced by i.p. administration of Thioacetamide (TAA), Through evaluation of plasma and brain Ammonia, serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT), Albumin, Total Protein, Total Bilirubin, Urea and Uric acid. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx), were determined in the liver and brain tissues. Extent of oxidative stress was also assessed by hepatic and brain lipid peroxides (MDA), in addition to brain nitric oxide (NO) and Monoamine oxidase (MAO). Thioacetamide induced a significant increase in 1) ALT, AST, ALP, γ-GT, Albumin; Total Protein, Total Bilirubin, Urea and Uric acid Levels in serum, 2) plasma and brain ammonia level 3) brain NO level, 4) liver and brain MDA. Also marked depletion in liver and brain GSH, CAT, SOD, GPx and brain MAO were observed after TAA intoxication. Rutin and Resveratrol Pretreatment was able to mitigate hepatic and brain damage induced by TAA and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status and antioxidant enzymes toward control levels. Pretreatment of rutin and resveratrol was highly effective and protective against TAA induced hepatic encephalopathy. The results of the present study suggest that rutin and resveratrol have potential to exert curative effects against liver injury.
Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malign... more Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation. The chemopreventive effect of silymarin on inflammatory markers and oxidative damage, caspase-3 and antioxidant status as well as the histopathological alterations in hepatic tissue in N-nitrosodiethylamine (DEN)-induced hepatic carcinogenesis in male albino rats was investigated. To induce hepato cellular carcinoma, rats were given DEN injections (i.p, 200 mg/kg b.wt.) three times at a 15 days interval. Seventy five rats divided into five equal groups. Group Ι :(Control group): received no drugs. Group Π :(DEN group). Group III :(DEN + silymarin protected group): orally received silymarin (37.8mg/kg b. wt/day) one week before DEN injection and continued to be 13 weeks. Group IV :(DEN + silymarin treated group): Injected with DEN then orally treated with silymarin from the 8th week till the end of the experiment (13th week). Group V: (normal-silymarin group): received silymarin. Blood samples and liver tissues were collected from all experimental groups at the end of experiment on 13th week. The obtained results showed that, DEN-induced hepatic carcinogenesis significantly decreased super oxide dismutase (SOD) and Catalase (CAT) activities in liver tissue. On the other hand, a marked increase in liver tissue L-Malondialdhyde (L-MDA), DNA fragmentation percent, caspase-3 and nuclear factor-kappa beta (NF-κB) and in serum AFP, IL-6 and TNF-α levels were observed in DEN injected rats. silymarin was able to mitigate liver tissue damage induced by DEN through increasing of SOD and CAT activities in addition to decreasing DNA fragmentation percent, L-MDA, caspase-3 and NF-κB and nuclear factor kappa B P65. These data suggest that silymarin exhibited significant protection against DEN-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.
An excessive amount of thyroid hormone is produced by an overactive thyroid gland, which keeps th... more An excessive amount of thyroid hormone is produced by an overactive thyroid gland, which keeps the body active. This study was carried out to investigate how hyperthyroidismprompted liver damage and apoptosis could be alleviated with spirulina platensis and grape seed proanthocyanin extract in rats. Forty-eight male rats were divided into six groups. Group 1: received no drug. Group2 (hyperthyroidism): Rats received L-Thyroxine at dose of (50, 100, 200 ug/kg b.wt) orally for first three weeks of study, respectively. Group3 (GSPE Protected): Rats received GSPE (150/kg b. wt/day) for the first 3 weeks, then continued administered with L-Thyroxine for other 3 weeks. Group 4 (GSPE treated): Rats administered a daily dose of L-Thyroxinen for 3 weeks, followed by GPSE (150/kg b. wt/day) for another 3 weeks. Group 5 (Spirulina Protected); Rats received Spirulina and L-Thyroxine as in group III. Group 6 (Spirulina treated): Rats received Spirulina and L-Thyroxine similar to group IV. The data obtained demonstrated a substantial rise in serum T3 and T4 with marked decrease in TSH concentrations in hyperthyroid rats. A significant upregulation in miRNA 224 and downregulation in liver Protein kinase C alpha and miRNA 382 were observed in hyperthyroid rats. However, a significant decrease in T3, T4 and miRNA 224 with significant upregulation of miRNA 382 and PKCα and TSH level were observed after Spirulina and GPSE treatment and protection. In conclusion, GSPE and Spirulina platensis had a potential therapeutic and protective effect in Hyperthyroidism, through direct inactivation of T4 to T3 and mitigate micro-RNA and PKCα that essential for thyroid hormone homeostasis and thyroid functions. Hyperthyroidism GSPE Spirulina Thyroid hormones Micro-RNA
Spirulina and Grape Seed Proanthocyanidin Extract (GSPE) were studied for their potential therape... more Spirulina and Grape Seed Proanthocyanidin Extract (GSPE) were studied for their potential therapeutic and protective properties in hypothyroidism-induced rats. Six equal groups of forty-eight rats were formed. Group 1is a control and Group 2 (hypothyroidism) received an oral dose of carbimazole (1.8 mg/kg b.wt.) every day. Rats in Group3 (GSPE Protected) got (150/kg b. wt) of GSPE per day for the first 3 weeks, then continued administered with carbimazole for another 3 weeks. Group 4 (carbimazole + GSPE treated): Rats were administered a daily dose of carbimazole (1.8mg/kg b.wt) for 3 weeks, followed by GPSE (150/kg b. wt/day) for another 3 weeks. Group 5 (Spirulina Protected); Rats received Spirulina (300 mg/kg body weight per day) for the first three weeks, then continued with carbimazole for another 3 weeks. Group 6 (Spirulina treated): Rats administered a daily dose of carbimazole for 3 weeks, followed by Spirulina (300/kg b. wt/day) for other 3 weeks. The results collected demonstrated a significant rise in liver Caspase-8 gene expression in the hypothyroidism group along with significant increases in blood TSH, total cholesterol, and triacylglycerols. However, serum T3, T4 levels drastically dropped along with Bcl2 expression in the liver tissue. Treatment and protection of spirulina and GPSE reduced TSH, total cholesterol, triacylglycerols and Caspase-8 with significant upregulation of Bcl-2 and marked decrease in total cholesterol and triacylglycerols concentrations. In conclusion, grape seed extracts and Spirulina platensis had therapeutic potential in hypothyroidism, protect liver damage and mitigate Thyroid disruptors via anti-apoptotic activities. Hypothyroidism GSPE Spirulina Thyroid hormones Apoptosis
Hyper-or Hypothyroidism is an overactive or underactive thyroid gland that prevents the body from... more Hyper-or Hypothyroidism is an overactive or underactive thyroid gland that prevents the body from operating properly. The potential therapeutic effects of spirulina platensis and GSPE on experimental hypothyroidism and hyperthyroidism in rats were evaluated. A total 96 rats were divided into two main experimental groups: Experiment A: carbimazole-induced hypothyroidism (1.8 mg/kg b. wt.) and experiment B: induced hyperthyroidism (50, 100, 200 µg/kg b. wt.) for the first three weeks, respectively. The administered GSPE dose (150mg /kg b. wt./day) and Spirulina (300 mg/kg b. wt./day) for 3 weeks. The hyperthyroidism experiment (A) six sets of rats were used: Group 1 (control normal), Group 2 (hyperthyroidism), Group 3 (GSPE Protected): GSPE administered for the first 3 weeks and continued with thyroxine for another 3 weeks. Group 4 (GSPE treated): thyroxine administered for 3 weeks, followed by GPSE as in group 3. Group 5 (Spirulina Protected); spirulina and thyroxine administration as in group 3. Group 6 (Spirulina treated): spirulina and thyroxine administration in group IV. The hypothyroidism experiment (B) rats divided also into 6 groups like to the above design in hyperthyroidism experiment (A) but carbimazole dose was stable (1.8 mg/kg b. wt.) in the 3 weeks. In hyperthyroidism spirulina and GPSE significantly increased serum total cholesterol, triacylglycerols with down regulation of liver Caspase-8 and significant upregulation of Bcl2 gene. In hypothyroidism spirulina and GPSE exhibited down regulation in liver miRNA 224, PKCα with significant upregulation of miRNA 382 gene in hypothyroid rats. Spirulina and grape seed may treat and prevent hyperthyroidism or hypothyroidism in rats. Hyperthyroidism Hypothyroidism MicroRNA.
Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocogn... more Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid β (Aβ). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3β)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1β (IL-1β) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer's disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways.
Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitiv... more Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminumchloride (AlCl 3) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid β (Aβ). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3β)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1β (IL-1β) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer's disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways.
Background: Diabetes mellitus represents a global health problem. It characterized by hyperglycem... more Background: Diabetes mellitus represents a global health problem. It characterized by hyperglycemia that induces oxidative stress leading to a generation of free radicals. A wide variety of natural products in plants and other marine animals represent antioxidant activity and other health benefits like those of sea cucumber. Therefore, this study aimed to investigate the antidiabetic activity of glycosidic compoundsaponinderived from the Egyptian sea cucumber, Holothuria thomasi. Materials and methods: Saponin has been extracted from the Egyptian sea cucumber and confirmed by hemolysis, Salkowski tests, FT/IR, UV and GC-MS analysis. Eighty white female albino rats were divided into four equal groups. The first two groups of rats; control normal and control normal saponin-treated groups. The last two groups which were made diabetic by intraperitoneal injection of streptozotocin had one diabetic control and the other diabetic group that got 300 mg/kg B.wt. of saponin extract after Thirty-five days after diabetes induction and lasted for six weeks. Results: The functional group of saponin extract which established with FT/IR spectroscopy demonstrated the presence of saponin in the extracted materials as shown in the peak of the functional group in relevance to the standard one. The UV spectra revealed that l max of saponin extract was 282 nm which in accordance to the standard saponin. Also, GC-MS analysis indicated that the aglycone part of saponin was methyl esters of octadecanoic acid. Saponin extract significantly decreased serum glucose, a-amylase activity, adiponectin, IL-6, TNF-a concentrations and liver L-MDA. However, serum insulin and liver glycogen levels were significantly increased as compared with the diabetic non-treated groups. The histopathological results supported that saponin extract markedly reduced the degenerative change in b-cells. Conclusions: This study, therefore, depicts that the Egyptian Holothuria thomasi, sea cucumber saponin as a hypoglycemic agent with the potential to normalize aberrant biochemical parameters and preserved the normal histological architecture of the islets cells of pancreatic tissues. 2016 Elsevier Masson SAS. All rights reserved.
Chemotherapeutic drugs, particularly alkylating cytotoxics such as cyclophosphamide (CYP) play a ... more Chemotherapeutic drugs, particularly alkylating cytotoxics such as cyclophosphamide (CYP) play a great job in inducing premature ovarian failure (POF). Hormone replacement therapy (HRT) is a widely used medication to improve hormone secretion. However, long-term HRT increases the risk of breast cancer and cardiovascular disease is concerning. Therefore, there is an urgent need to develop a safe and effective treatment for POF. Bone Marrow-(BM-MSCs) and Umbilical Cord-(UC-MSCs) derived stem cells (SCs) were isolated and identified from healthy rats. For POF induction, CYP (200mg/Kg b.wt) injected (i.p) into CYP, CYP+BMSCs, and CYP+UCMSCs followed by another dose (10mg/ b.wt, i.p) after one week. The normal control (NC) group were injected with saline. After two weeks of POF induction MSCs (1 × 10 6 cells/ml) of media were transplanted into POF rats through tail-vein. The effects of MSCs transplantation to POF were evaluated through sex hormones, iron, and complete blood count (CBC) analysis. POF-induced rats showed a significant increase in serum FSH and LH, with marked decrease in anti-Mullerian hormone (AMH) and estradiol (E2). Obvious increase in serum iron level observed in CYP group compared to the NC. Moreover, POF-induced rats displayed leucopenia, erythrocytopenia, and thrombocytopenia with a significant reduction in Hb, PCV, MCV, MCH, and MCHC compared to the NC. Administration of MSCs to CYPinjured rats significantly improved female reproductive hormones disturbances, iron, and hemogram. It was suggested that MSCs was a potential approach for improving sex hormones, iron, and hematological alterations, and potentially promoting the restoration of CYP-induced POF.
Premature ovarian failure (POF) contributes significantly to female infertility in young women. I... more Premature ovarian failure (POF) contributes significantly to female infertility in young women. It mainly developed after chemotherapy medication, particularly with alkylating cytotoxic such as cyclophosphamide (CYP). The present study was designed to determine the advantages of mesenchymal stem cells (MSCs) as therapy for POF conditions in female rat models. For POF induction, CYP (200mg/Kg b.wt) was injected intraperitoneally (i.p) followed by another activation dose of CYP (10mg/ b.wt, i.p) after one week. MSCs treatment was enhanced by Bone Marrow-derived stem cells (BM-MSCs) or Umbilical Cord-derived stem cells (UC-MSCs) after two weeks of POF induction. The normal control (NC) group rats were injected with saline. The effects of POF modeling and MSCs (1 × 10 6 cells) transplantation through tail-vein were examined by sex hormonal analysis and morphological examination of ovarian follicles. CYP-induced rats POF showed a significant reduction in AMH and E2 concentrations in addition to total, primordial, primary, secondary, and mature graffian follicles in contrast to the NC group (P<0.0001). The FSH and LH concentrations were increased in the CYP group and degenerated follicles than in the NC group (P<0.0001). Transplanting MSCs improved the histopathological and hormonal analysis of the ovarian microenvironment induced by CYP (P<0.0001) with no significant difference in response to BM-MSCs or UC-MSCs. It was concluded that MSCs injection was a possible strategy for improving CYP-induced morphological changes, and sex-hormonal alterations, potentially promoting the restoration of CYP-induced infertility via POF.
A potential therapeutic impact of Gallic acid in a rat model of hepatocarcinogenesis through inhi... more A potential therapeutic impact of Gallic acid in a rat model of hepatocarcinogenesis through inhibition of cell proliferation and oncogenic miRNA-221 and induction of apoptosis by Nrf-2 /Bcl-2/TGF-β1 signaling pathways.
Hepatocellular carcinoma (HCC) accounting about 75% of hepatic neoplasia, making it the most comm... more Hepatocellular carcinoma (HCC) accounting about 75% of hepatic neoplasia, making it the most common kind of liver cancer worldwide. So, this study was planned to evaluate the beneficial chemopreventive efficacy of hesperidin (Hes) in experimental model of Diethyl nitrosamine (DEN) / Carbon tetrachloride (CCl 4)-induced HCC in rats. Thirty male rats were divided into 3 equal groups. Group 1 (normal control): rats didn't receive any treatment. Group 2 (HCC): HCC was induced in rats by injection of DEN (200mg/kg b.w/i.p), then 2 weeks later of DEN injection rats received 3 weekly successive doses of CCl 4 (3ml/kg b.wt/ orally) at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl 4 administration were repeated once again after 5 weeks. Group 3 (HCC+ hesperidin): 15 weeks after HCC induction, rats treated with Hes (150 mg/kg b.wt), orally and continued for 6 weeks. A significant increase in serum ALT, AST and ALP activities were observed in HCC-induced rats. However, significant downregulation of liver Nrf2, Caspase-3, Bcl-2 and MicroRNA-34a with upregulation of FGF-2 and MicroRNA-221 with Global DNA hyper-methylation were observed in HCC group. Hesperidin treatment exhibited downregulation of microRNA-221 and FGF-2 with upregulation of Nrf2, Bcl-2, caspase 3 gene and Global DNA hypo-methylation. Interestingly, improvement of liver histopathological alterations supported the chemopreventive activity of Hesperidin. Conclusively, Hesperidin ameliorates the progression of HCC and has promising chemopreventive, and antiangiogenic activity, inhibiting growth promoting oncogene and initiation of gene regulating apoptosis and protects the liver from oxidative damage and inflammation.
The antioxidative, anti-inflammatory, anticancer, and hepatoprotective qualities of ginger have b... more The antioxidative, anti-inflammatory, anticancer, and hepatoprotective qualities of ginger have been well-established. This research was purposed to evaluate both ginger extract (GE) and ginger nanoparticles (GNPs) potential chemotherapeutic influences in mitigating hepatocellular carcinoma (HCC) induced by carbon tetrachloride (CCl4) and diethylnitrosamine (DEN) in rats. HCC was induced in rats through DEN injection (200 mg/kg b.w./I.P.). Subsequently, after a two-week interval, rats were exposed to three consecutive weekly doses of CCL4 (3 mL/kg b.w. orally), prepared in a 1:1 dilution with corn oil, serving as a carcinogenic promoter. CCL4 and DEN administration were repeated following an additional 5-week interval. Fifteen weeks after HCC induction, oral treatment with GE (300 mg/kg b.w./day) and GNPs (50 mg/kg b.w./day) was initiated and continued for 6 weeks. Twenty-eight rats were divided evenly into four subgroups: G1 (normal control), G2 (DEN/CCL4 induced HCC), G3 (DEN/CCL4+GE), and G4 (DEN/CCL4+GNPs). The results demonstrated a substantial elevation in AST, ALT, and ALP serum activities and a decrease in liver microRNA-29 expression in rats with induced hepatocellular carcinoma. High levels of TGF-β1, FGF, and HGF also pointed to upregulation during the development of HCC. Treatment with GE and GNPs led to a significant reduction in liver marker enzymes and the heightened expression of TGF-β1, FGF2, and HGF, accompanied by an upregulation of microRNA-29 in rats with liver cancer. In conclusion, GE and GNP treatments may serve as chemotherapeutic agents by activating the tumor suppressor microRNA-29 gene and suppressing angiogenesis growth factors in the liver.
Hepatocellular carcinoma (HCC) is the second most fatal cancer, caused by either factors outside ... more Hepatocellular carcinoma (HCC) is the second most fatal cancer, caused by either factors outside the body or even with hereditary or genetic changes. The potential chemotherapeutic effect of ginger extract (GE) and ginger nanoparticles (GNPs) against diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) induced HCC in rats was evaluated. HCC was induced via utilizing DEN injection (200 mg/kg b. wt/ I.P), then 2 weeks later of DEN injection rats received 3 weekly successive doses of CCl4 diluted with corn oil at a ratio of 1:1(3ml/kg b.wt) orally to boost the carcinogenic impact. The administration of DEN and CCl4 was repeated after a period of 5 weeks. 15 weeks after HCC induction, treatment with GE (300mg/kg b.wt/day) and GNPs (50mg/kg b.wt/day) were given orally and continued for six weeks. Twenty-four male rats were separated into four equal groups. Group 1 (normal control): Rats received saline as a vehicle, Group 2: (DEN/CCl4 induced HCC), Group 3: (DEN/CCl4 +GE), and Group 4: (DEN/CCl4 +GNPs). The results revealed significant upregulation in liver microRNA-221 with obvious down-regulation of Nrf2 and Bcl-2 and insignificant downregulation in caspase 3 gene in HCC-induced rats. GE and GNPs treatment exhibited a significant decrease in liver marker enzymes with downregulation of microRNA-221 and upregulation of Nrf2, Bcl-2 and caspase 3 gene expression. These findings suggested that GE and GNPs have a beneficial therapeutic effect against liver cancer, inhibiting growthpromoting oncogene and increasing apoptosis.
The Hepatitis C virus causes acute and chronic hepatitis. Micro RNA could be used as disease biom... more The Hepatitis C virus causes acute and chronic hepatitis. Micro RNA could be used as disease biomarkers. This study looked into Micro RNA125b, Micro RNA 489-3p, and biochemical analysis as a diagnostic for HCV. This study included 20 individuals who had chronic liver disease and were admitted to the Gastroenterology Hospital in Mansoura and the Oncology Institute in Mansoura. All individuals were subjected to full clinical examinations. Following analysis of all patients, polymerase chain reaction (PCR) was confirmed to be positive for chronic HCV in 5 individuals. Five negative control samples were taken from a healthy control group of the same age range and sex. Serum liver function parameters and AFP with gene expression of microRNA125b and microRNA 489-3p were estimated. The HCV group significantly increased AST, ALT, DBIL, TBIL, ALP, GGT, and ALB) while significantly decreasing albumin concentrations. In the HCV group, AFP was substantially higher than in control. The HCV group had a considerable rise in miRNA125b (10.07+ 0.19) but a significant drop in miRNA489-3p (0.36+ 0.02). In addition to biochemical investigation, we found that miRNA125b and miRNA489-3p expression levels were employed as valuable markers for HCV diagnosis.
Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is ... more Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is the frequent reason for cirrhosis all over the world. MicroRNA could be used as a disease biomarker. This investigation was carried out to investigate mRNA-125b, mRNA 489-3p, and biochemical analysis as markers for chronic HBV. This work included 20 patients who had chronic liver disease admitted to the Gastroenterology Hospital and Oncology Institute in Mansoura. After investigation, serum samples were obtained from five patients that were positive for PCR chronic HBV. For control, negative serum samples were collected at the same age range and sex. Liver function and alpha fetoprotein (AFP) parameters were estimated. RNA was extracted from serum for gene expression of mRNA125b and mRNA 489-3p. The main results showed that the HBV group had a significant increase in ALT, AST, TBIL, GGT, ALP, and AFP, while there was a significant decrease in albumin levels compared to the control group. HBV group showed a significant increase (6.70 ± 0.18) in mRNA125b, but a significant decrease in mRNA489-3 (0.51±0.03). In conclusion, mRNA125b and mRNA489-3p expressions along with biochemical analysis could be used as accurate markers for HBV diagnosis. HBV MicroRNA 125b MicroRNA 489-3p
Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is ... more Hepatitis B virus (HBV) is a blood-borne virus that poses chief public health threats, and it is the frequent reason for cirrhosis all over the world. MicroRNA could be used as a disease biomarker. This investigation was carried out to investigate mRNA-125b, mRNA 489-3p, and biochemical analysis as markers for chronic HBV. This work included 20 patients who had chronic liver disease admitted to the Gastroenterology Hospital and Oncology Institute in Mansoura. After investigation, serum samples were obtained from five patients that were positive for PCR chronic HBV. For control, negative serum samples were collected at the same age range and sex. Liver function and alpha fetoprotein (AFP) parameters were estimated. RNA was extracted from serum for gene expression of mRNA125b and mRNA 489-3p. The main results showed that the HBV group had a significant increase in ALT, AST, TBIL, GGT, ALP, and AFP, while there was a significant decrease in albumin levels compared to the control group. HBV group showed a significant increase (6.70 ± 0.18) in mRNA125b, but a significant decrease in mRNA489-3 (0.51±0.03). In conclusion, mRNA125b and mRNA489-3p expressions along with biochemical analysis could be used as accurate markers for HBV diagnosis. HBV MicroRNA 125b MicroRNA 489-3p
Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species... more Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species (ROS) scavenger and good metal chelator, rich in phenolic hydroxyl groups that have strong antioxidant activity. For the present study, the strong antioxidant activity of QUR on several biochemical parameters in blood and liver of male rats exposed to high fat diet (HFD) induced non alcoholic steatohepatitis (NASH), were investigated. Sixty white male albino rats weighting 150-200 gm were used in this study. The rats were divided into four equal groups. 1) Normal group: received no drugs. 2) NASH group: received HFD daily for 12 weeks. 3) NASH + Quercetin group: received HFD daily for 3 months then QUR treatment (50 mg/kg body weight) through intraperitoneal route (i.p) daily for 10 weeks after induction of NASH. Blood and liver samples were collected from all animal groups two times, after the 6 th and 10 th week of treatment period. Serum was separated for determination of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). The obtained results revealed that, HFD supplementation exhibited a significant increase in: 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. QUR administration in NASH rats exhibited a significant increase in all mentioned parameters. On contrast, HFD supplementation exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed. QUR administration in NASH rats exhibited significant increase in all mentioned parameters. From the obtained results, it could be concluded that, the potential of QUR as natural antioxidant act as a powerful agent against the harmful effects of NASH.
Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species... more Quercetin (QUR) is a polyphenolic phytochemical flavonoid, it is a strong reactive oxygen species (ROS) scavenger and good metal chelator, rich in phenolic hydroxyl groups that have strong antioxidant activity. For the present study, the strong antioxidant activity of QUR on several biochemical parameters in blood and liver of male rats exposed to high fat diet (HFD) induced non alcoholic steatohepatitis (NASH), were investigated. Sixty white male albino rats weighting 150-200 gm were used in this study. The rats were divided into four equal groups. 1) Normal group: received no drugs. 2) NASH group: received HFD daily for 12 weeks. 3) NASH + Quercetin group: received HFD daily for 3 months then QUR treatment (50 mg/kg body weight) through intraperitoneal route (i.p) daily for 10 weeks after induction of NASH. Blood and liver samples were collected from all animal groups two times, after the 6 th and 10 th week of treatment period. Serum was separated for determination of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). The obtained results revealed that, HFD supplementation exhibited a significant increase in: 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. QUR administration in NASH rats exhibited a significant increase in all mentioned parameters. On contrast, HFD supplementation exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed. QUR administration in NASH rats exhibited significant increase in all mentioned parameters. From the obtained results, it could be concluded that, the potential of QUR as natural antioxidant act as a powerful agent against the harmful effects of NASH.
Non alcoholic steatohepatitis (NASH) is a pathological condition characterized by accumulation of... more Non alcoholic steatohepatitis (NASH) is a pathological condition characterized by accumulation of lipids in the liver of non alcoholic individuals and consequent oxidative stress leading to cirrhosis of liver in the long run. Silymarin is a unique flavonoid complex extract isolated from seeds of the milk thistle plant (Silybum marianum) and has strong antioxidant and radical scavenging properties. The present research aimed to evaluate the therapeutic effects of silymarin (Slym) as natural antioxidant and anti-inflammatory on liver tissue of male rats exposed to experimental model of non alcoholic steatohepatitis (NASH) induced by supplementation of high fat diet (HFD) for 3 months, Through evaluation of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT) activities and Albumin, Total Protein, Total Bilirubin, Total Cholesterol and triglycerides concentrations. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD) and Catalase (CAT), were determined in liver tissues. Extent of oxidative stress was also assessed by hepatic lipid peroxides (MDA). HFD supplementation induced a significant increase in 1) serum ALT, AST, ALP and γ-GT activities, in addition to Total Bilirubin, Total Cholesterol and triglycerides concentrations. 2) Liver MDA concentration. On contrast, it exhibited a significant decrease in serum Albumin and Total Protein, also marked depletion in liver GSH, CAT and SOD, were observed after HFD supplementation. Silymarin treatment was able to mitigate and ameliorate hepatic NASH induced by HFD and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status and antioxidant enzymes toward control levels. Silymarin treatment was highly effective against HFD induced NASH. The results of the present study suggest that silymarin has the potential to exert curative effects against liver NASH.
The present research aimed to evaluate the hepato/neuroprotective effects of Rutin and Resveratro... more The present research aimed to evaluate the hepato/neuroprotective effects of Rutin and Resveratrol as natural antioxidants on brain and liver tissues of experimental rats exposed to acute liver failure induced by i.p. administration of Thioacetamide (TAA), Through evaluation of plasma and brain Ammonia, serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Gamma Glutamyl-Transferase (γ-GT), Albumin, Total Protein, Total Bilirubin, Urea and Uric acid. Levels of reduced glutathione (GSH) and activities of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx), were determined in the liver and brain tissues. Extent of oxidative stress was also assessed by hepatic and brain lipid peroxides (MDA), in addition to brain nitric oxide (NO) and Monoamine oxidase (MAO). Thioacetamide induced a significant increase in 1) ALT, AST, ALP, γ-GT, Albumin; Total Protein, Total Bilirubin, Urea and Uric acid Levels in serum, 2) plasma and brain ammonia level 3) brain NO level, 4) liver and brain MDA. Also marked depletion in liver and brain GSH, CAT, SOD, GPx and brain MAO were observed after TAA intoxication. Rutin and Resveratrol Pretreatment was able to mitigate hepatic and brain damage induced by TAA and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status and antioxidant enzymes toward control levels. Pretreatment of rutin and resveratrol was highly effective and protective against TAA induced hepatic encephalopathy. The results of the present study suggest that rutin and resveratrol have potential to exert curative effects against liver injury.
Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malign... more Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation. The chemopreventive effect of silymarin on inflammatory markers and oxidative damage, caspase-3 and antioxidant status as well as the histopathological alterations in hepatic tissue in N-nitrosodiethylamine (DEN)-induced hepatic carcinogenesis in male albino rats was investigated. To induce hepato cellular carcinoma, rats were given DEN injections (i.p, 200 mg/kg b.wt.) three times at a 15 days interval. Seventy five rats divided into five equal groups. Group Ι :(Control group): received no drugs. Group Π :(DEN group). Group III :(DEN + silymarin protected group): orally received silymarin (37.8mg/kg b. wt/day) one week before DEN injection and continued to be 13 weeks. Group IV :(DEN + silymarin treated group): Injected with DEN then orally treated with silymarin from the 8th week till the end of the experiment (13th week). Group V: (normal-silymarin group): received silymarin. Blood samples and liver tissues were collected from all experimental groups at the end of experiment on 13th week. The obtained results showed that, DEN-induced hepatic carcinogenesis significantly decreased super oxide dismutase (SOD) and Catalase (CAT) activities in liver tissue. On the other hand, a marked increase in liver tissue L-Malondialdhyde (L-MDA), DNA fragmentation percent, caspase-3 and nuclear factor-kappa beta (NF-κB) and in serum AFP, IL-6 and TNF-α levels were observed in DEN injected rats. silymarin was able to mitigate liver tissue damage induced by DEN through increasing of SOD and CAT activities in addition to decreasing DNA fragmentation percent, L-MDA, caspase-3 and NF-κB and nuclear factor kappa B P65. These data suggest that silymarin exhibited significant protection against DEN-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.
An excessive amount of thyroid hormone is produced by an overactive thyroid gland, which keeps th... more An excessive amount of thyroid hormone is produced by an overactive thyroid gland, which keeps the body active. This study was carried out to investigate how hyperthyroidismprompted liver damage and apoptosis could be alleviated with spirulina platensis and grape seed proanthocyanin extract in rats. Forty-eight male rats were divided into six groups. Group 1: received no drug. Group2 (hyperthyroidism): Rats received L-Thyroxine at dose of (50, 100, 200 ug/kg b.wt) orally for first three weeks of study, respectively. Group3 (GSPE Protected): Rats received GSPE (150/kg b. wt/day) for the first 3 weeks, then continued administered with L-Thyroxine for other 3 weeks. Group 4 (GSPE treated): Rats administered a daily dose of L-Thyroxinen for 3 weeks, followed by GPSE (150/kg b. wt/day) for another 3 weeks. Group 5 (Spirulina Protected); Rats received Spirulina and L-Thyroxine as in group III. Group 6 (Spirulina treated): Rats received Spirulina and L-Thyroxine similar to group IV. The data obtained demonstrated a substantial rise in serum T3 and T4 with marked decrease in TSH concentrations in hyperthyroid rats. A significant upregulation in miRNA 224 and downregulation in liver Protein kinase C alpha and miRNA 382 were observed in hyperthyroid rats. However, a significant decrease in T3, T4 and miRNA 224 with significant upregulation of miRNA 382 and PKCα and TSH level were observed after Spirulina and GPSE treatment and protection. In conclusion, GSPE and Spirulina platensis had a potential therapeutic and protective effect in Hyperthyroidism, through direct inactivation of T4 to T3 and mitigate micro-RNA and PKCα that essential for thyroid hormone homeostasis and thyroid functions. Hyperthyroidism GSPE Spirulina Thyroid hormones Micro-RNA
Spirulina and Grape Seed Proanthocyanidin Extract (GSPE) were studied for their potential therape... more Spirulina and Grape Seed Proanthocyanidin Extract (GSPE) were studied for their potential therapeutic and protective properties in hypothyroidism-induced rats. Six equal groups of forty-eight rats were formed. Group 1is a control and Group 2 (hypothyroidism) received an oral dose of carbimazole (1.8 mg/kg b.wt.) every day. Rats in Group3 (GSPE Protected) got (150/kg b. wt) of GSPE per day for the first 3 weeks, then continued administered with carbimazole for another 3 weeks. Group 4 (carbimazole + GSPE treated): Rats were administered a daily dose of carbimazole (1.8mg/kg b.wt) for 3 weeks, followed by GPSE (150/kg b. wt/day) for another 3 weeks. Group 5 (Spirulina Protected); Rats received Spirulina (300 mg/kg body weight per day) for the first three weeks, then continued with carbimazole for another 3 weeks. Group 6 (Spirulina treated): Rats administered a daily dose of carbimazole for 3 weeks, followed by Spirulina (300/kg b. wt/day) for other 3 weeks. The results collected demonstrated a significant rise in liver Caspase-8 gene expression in the hypothyroidism group along with significant increases in blood TSH, total cholesterol, and triacylglycerols. However, serum T3, T4 levels drastically dropped along with Bcl2 expression in the liver tissue. Treatment and protection of spirulina and GPSE reduced TSH, total cholesterol, triacylglycerols and Caspase-8 with significant upregulation of Bcl-2 and marked decrease in total cholesterol and triacylglycerols concentrations. In conclusion, grape seed extracts and Spirulina platensis had therapeutic potential in hypothyroidism, protect liver damage and mitigate Thyroid disruptors via anti-apoptotic activities. Hypothyroidism GSPE Spirulina Thyroid hormones Apoptosis
Hyper-or Hypothyroidism is an overactive or underactive thyroid gland that prevents the body from... more Hyper-or Hypothyroidism is an overactive or underactive thyroid gland that prevents the body from operating properly. The potential therapeutic effects of spirulina platensis and GSPE on experimental hypothyroidism and hyperthyroidism in rats were evaluated. A total 96 rats were divided into two main experimental groups: Experiment A: carbimazole-induced hypothyroidism (1.8 mg/kg b. wt.) and experiment B: induced hyperthyroidism (50, 100, 200 µg/kg b. wt.) for the first three weeks, respectively. The administered GSPE dose (150mg /kg b. wt./day) and Spirulina (300 mg/kg b. wt./day) for 3 weeks. The hyperthyroidism experiment (A) six sets of rats were used: Group 1 (control normal), Group 2 (hyperthyroidism), Group 3 (GSPE Protected): GSPE administered for the first 3 weeks and continued with thyroxine for another 3 weeks. Group 4 (GSPE treated): thyroxine administered for 3 weeks, followed by GPSE as in group 3. Group 5 (Spirulina Protected); spirulina and thyroxine administration as in group 3. Group 6 (Spirulina treated): spirulina and thyroxine administration in group IV. The hypothyroidism experiment (B) rats divided also into 6 groups like to the above design in hyperthyroidism experiment (A) but carbimazole dose was stable (1.8 mg/kg b. wt.) in the 3 weeks. In hyperthyroidism spirulina and GPSE significantly increased serum total cholesterol, triacylglycerols with down regulation of liver Caspase-8 and significant upregulation of Bcl2 gene. In hypothyroidism spirulina and GPSE exhibited down regulation in liver miRNA 224, PKCα with significant upregulation of miRNA 382 gene in hypothyroid rats. Spirulina and grape seed may treat and prevent hyperthyroidism or hypothyroidism in rats. Hyperthyroidism Hypothyroidism MicroRNA.
Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocogn... more Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid β (Aβ). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3β)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1β (IL-1β) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer's disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways.
Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitiv... more Alzheimer's disease (AD) is a brain disorder associated with a gradual weakening in neurocognitive functions, neuroinflammation, and impaired signaling pathways. Resveratrol (RSV) has neuroprotective properties, but with low bioavailability, and low solubility in vivo. Selenium (Se) is an essential micronutrient for brain function. Thus, this study aimed to evaluate the role of formulated RSV-Se nanoparticles (RSV-SeNPs) on neurochemical and histopathological approaches associated with the AD model in rats induced by Aluminumchloride (AlCl 3) at a dose of 100 mg/kg/day for 60 days. RSV-SeNPs supplementation attenuates the impaired oxidative markers and mitochondrial dysfunction. The ameliorative effect of RSV-SeNPs on cholinergic deficits was associated with clearance of amyloid β (Aβ). Furthermore, activation of phosphatidylinositol 3 kinase (PI3K) deactivates glycogen synthase kinase 3 beta (GSK-3β)-mediated tau hyperphosphorylation. Additionally, RSV-SeNPs downregulate signal transducer and activator of transcription (STAT3) expression as well as interleukin-1β (IL-1β) levels, therefore alleviating neuroinflammation in AD. Moreover, RSV-SeNPs upregulate the expression of Sirtuin-1 (SIRT1) and lower that of microRNA-134, consequently increasing neurite outgrowth. Eventually, the obtained results showed that nano-formulation of resveratrol with selenium maximized the therapeutic potential of RSV against Alzheimer's disease not only by their antioxidant but also by anti-inflammatory effect improving the neurocognitive function and modulating the signaling pathways.
Background: Diabetes mellitus represents a global health problem. It characterized by hyperglycem... more Background: Diabetes mellitus represents a global health problem. It characterized by hyperglycemia that induces oxidative stress leading to a generation of free radicals. A wide variety of natural products in plants and other marine animals represent antioxidant activity and other health benefits like those of sea cucumber. Therefore, this study aimed to investigate the antidiabetic activity of glycosidic compoundsaponinderived from the Egyptian sea cucumber, Holothuria thomasi. Materials and methods: Saponin has been extracted from the Egyptian sea cucumber and confirmed by hemolysis, Salkowski tests, FT/IR, UV and GC-MS analysis. Eighty white female albino rats were divided into four equal groups. The first two groups of rats; control normal and control normal saponin-treated groups. The last two groups which were made diabetic by intraperitoneal injection of streptozotocin had one diabetic control and the other diabetic group that got 300 mg/kg B.wt. of saponin extract after Thirty-five days after diabetes induction and lasted for six weeks. Results: The functional group of saponin extract which established with FT/IR spectroscopy demonstrated the presence of saponin in the extracted materials as shown in the peak of the functional group in relevance to the standard one. The UV spectra revealed that l max of saponin extract was 282 nm which in accordance to the standard saponin. Also, GC-MS analysis indicated that the aglycone part of saponin was methyl esters of octadecanoic acid. Saponin extract significantly decreased serum glucose, a-amylase activity, adiponectin, IL-6, TNF-a concentrations and liver L-MDA. However, serum insulin and liver glycogen levels were significantly increased as compared with the diabetic non-treated groups. The histopathological results supported that saponin extract markedly reduced the degenerative change in b-cells. Conclusions: This study, therefore, depicts that the Egyptian Holothuria thomasi, sea cucumber saponin as a hypoglycemic agent with the potential to normalize aberrant biochemical parameters and preserved the normal histological architecture of the islets cells of pancreatic tissues. 2016 Elsevier Masson SAS. All rights reserved.
Citation: Hussein SA, Ahmed TE, Amin A, Ali AH. The anti-inflammatory and anti-apoptotic role of ... more Citation: Hussein SA, Ahmed TE, Amin A, Ali AH. The anti-inflammatory and anti-apoptotic role of crocin against expression of MMp-9, TIMP-1, MCP-1, Caspase-3, PPARα in heart tissue, and metamorphoses of MicroRNA 188 in hyperhomocysteinemic rats. Abstract Crocin (a water-soluble carotenoid) is the most abundant antioxidant among active constituents of Crocus sativus. Crocin has protective effects on brain, skeletal muscle, and kidney ischemia-reperfusion injury models via its antioxidant properties. The protective and anti-inflammatory effect of crocin against L-methionine-induced hyperhomocysteinemia (HHcy) in rats was evaluated. Thirty male albino rats were divided into three equal groups. Group I (control normal): rats fed ordinary diet without any treatment. Group II (L-methionine-induced HHcy): rats received L-methionine (1.7 g/kg body weight/day) orally for 8 weeks continuously. Group III (HHcy 1 crocin): rats received crocin in dose (50 mg/kg body weight/day, I.P.) for 4 weeks after induction of HHcy. The results obtained showed a significant increase in serum Hcy concentration and upregulation of NF-kβ gene expression in liver tissue and also in the gene expression level of TIMP-1, MMp-9, MCP-1, Caspase-3, and PPARα in heart tissues with significant downregulation of serum miRNA188 gene expression level in hyperhomocysteinemic (HHcy) rats. However, crocin treatment to HHcy induced in rats significantly improved all previous indicators to its normal ranges. The histopathological findings revealed that crocin treatment markedly reduced the HHcy-induced pathological changes and displayed marked improvement with normal histological architecture of the heart and brain tissues. These results suggested that crocin had a potentially ameliorating role with powerful anti-inflammatory and anti-apoptotic effects on cardiac tissue, as revealed by suppression of proinflammatory mediators and secretion through inhibition of NF-kB signaling pathways, which may lead to upregulated miR-188 gene expression, suppress proapoptotic Caspase-3, and may protect from heart tissue injury against HHcy.
Uploads
Papers by Samy Aziza