Physiology

Background:A defective mucus composition represents a key pathogenetic factor for intestinal injury. Phosphatidylcholine (PC) is an essential component contributing to formation of a hydrophobic mucous layer. For evaluation of phosphatidylcholine in the pathogenesis of ulcerative colitis, the concentration and composition of PC in the rectal mucus of patients with inactive ulcerative colitis was determined. Electrospray ionization (ESI) tandem spectroscopy (MS/MS) allows quantification of phosphatidylcholine species and enables us first time to analyze crude extracts on a pmol level. Methods: Phosphatidylcholine and lysophosphatidylcholine (LPC) species from rectoscopically acquired mucus aliquots of patients with inactive ulcerative colitis were analyzed by nano-ESI MS/MS and quantified with internal standardization. For evaluation of the origin of intestinal PC we used a mice model with absent biliary phospholipid secretion (mdr2 (-/-)mice). In comparison to normal controls (mdr2 (+/+) mice), mucus PC composition was determined in different segments of the gut. Results: Patients with inactive ulcerative colitis showed significant less PC and LPC in rectal mucus (1105 _+ 813 pmol/mg dry weight) compared to control subjects (307 -+ 414 pmol/mg dry weight). The quality of PC and LPC species was not significant different in both groups. We found in about 90 % unsaturated PC species (PC 16:0/18:1; PC 16:0/18:2; PC 18:0/18:1; PC 18:0/18:2; LPC 16:0; LPC 18:0). In mdr2 (-/-) mice and control animals no significant difference in PC composition was found, indicating that luminal PC is of intestinal and not biliary origin. Conclusion: Nano-ESI MS/MS is a suitable tool to analyze and quantify small amounts of PC in human mucus. Patients with ulcerative colitis have significant less PC in their intestinal mucus despite a comparable PC species composition pattern. This indicates that impaired intestinal PC secretion is a characteristic feature in ulcerative colitis and may predispose to an impaired mucosal barrier function facilitating inflammatory attacks by noxious colonic contents. The work was supported by a grant of the Dietmar Hopp Foundation.

We aimed to investigate the effects of electric shock (ES) on the course of experimental colitis and the involvement of possible central and peripheral mechanisms. In Sprague -Dawley rats (n = 190) colitis was induced by intracolonic administration 2,4,6-trinitrobenzenesulfonic acid (TNBS). The effects of ES (0.3 -0.5 mA) or the central administration of corticotropin-releasing factor (CRF; astressin, 10 Ag/kg) or cholecystokinin (CCK B ; 20 Ag/kg) receptor antagonists and peripheral glucocorticoid receptor (RU-486; 10 mg/kg) or ganglion (hexamethonium; 15 mg/kg) blockers on TNBS-induced colitis were studied by the assessment of macroscopic score, histological analysis and tissue myeloperoxidase activity. ES reduced all colonic damage scores (p < 0.05 -0.01), while central CRF (p < 0.05 -0.001) and CCK B receptor (p < 0.05 -0.01) blockers or peripheral hexamethonium (p < 0.05 -0.01) and RU-486 (p < 0.05) reversed stress-induced improvement. ES demonstrated an anti-inflammatory effect on colitis, which appears to be mediated by central CRF and CCK receptors with the participation of hypothalamo-pituitary-adrenal axis and the sympathetic nervous system. D

Cholestasis, which results in hepatic cell death, fibrosis, cirrhosis, and eventually liver failure, is associated with oxidative stress. The aim of this study was to evaluate the effects of milk thistle (MT, Silybum marianum) and ursodeoxycholic acid (UDCA) or their combination on the activation of hepatic stem cells and on the severity of cholestasis liver injury in rats. Under anesthesia, bile ducts of female Sprague Dawley rats were ligated (BDL) or had sham operation. BDL rats were administered saline, UDCA (15 mg/kg/d), MT (600 mg/kg/d), or UDCA+MT by gavage for 10 days. On the 11th day, rats were sacrificed and blood and liver samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) levels, and myeloperoxidase (MPO) activity were measured. Hepatic injury, a-smooth muscle actin expression, and stem cell markers c-kit, c-Myc, Oct3/4, and SSEA-1 were histologically determined. Histological scores, serum ALT, and...

Hyaluronic acid (HA) constitutes one of the major components of the extracellular matrix domain in almost all mammals. The aim of this study was to evaluate the regenerative capacity of HA matrix in rat calvarial bone defects and compare with those of different combinations of resorbable collagen membrane (M) and bovine-derived xenograft (G). Twenty-four 3-month-old male Sprague-Dawley rats weighing 200-250 g were included. Control group was created by leaving one defect empty from 2 critical size defects with 5 mm diameter formed in the calvarial bones of 8 rats. In the same rats, the other defect was treated with HA matrix alone. One of the 2 defects formed in other 8 rats was treated with HA+G and the other with HA+M. One of the 2 defects formed in the remaining 8 rats was treated with G+M and the other with HA+G+M. The animals were sacrificed at 4 weeks. Histologic, histomorphometric, and immunohistochemical analyses were performed. Both HA matrix alone and its combinations with...

Objective: Exercise has many beneficial effects in the treatment and prevention of Type 2 Diabetes Mellitus (T2DM). The aim of this study was to evaluate the effect of physical activities with different frequencies performed within a total total duration of one week on the heart and kidney tissues and vascular endothelial growth factor (VEGF) expressions in experimental T2DM model. Method: Rats (n: 30) were divided into sedentary control (SC), sedentary T2DM (SD), T2DM and continuous exercise (DEc, 30 min/day, 5 days/week), T2DM and short bouts exercise (DEsb, 3x10 min/day, 5 days/week), T2DM and weekend warrior exercise (DEww, 35+40 min/day, 2 days/week) groups. Rats were administered streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) through intraperitoneal route. After 6-weeks of swimming exercise (total duration 150 min/week), biochemical analyzes were performed to measure oral glucose tolerance test, insulin sensitivity and cytokines. Histopathological and immunohistochemical analyses [VEGF, capillary density, Transforming growth factor beta (TGF-β)] were performed in heart and kidney tissues. Results: Compared with sedentary T2DM rats, significant improvements were observed in all exercise groups in terms of blood glucose level, insulin sensitivity, capillary density in heart tissue, VEGF expressions in tissues, TGF-β expressions in kidney tissue and all histopathological analysis (p<0.05). Conclusion: This study shows that physical activity at various frequencies may significantly ameliorate harmful effects of T2DM on heart and kidney tissue without significant differences between exercise frequencies, provided that the total duration of aerobic exercise remains the same (150 min/week).

Effect of exercise and sildenafil on anxiety and cognition was examined. • Protection from acute stress will improve cognitive functions. • Chronic exercise and sildenafil improved stress status and cognitive functions. • Sildenafil treatment protected from inflammatory changes induced by acute stress. • Chronic exercise attenuated inflammatory status provoked by stress.

Objective: This study aims to investigate the effect of Momordica charantia L. (MoC) ethanolic extract on ulcerative colitis (UC) and was explored in vitro and in vivo. Materials and Methods: The rats were divided into control (C), saline-treated colitis (AA), MoC extract-treated colitis (AA+MoC), and sulfasalazine (SS)-treated colitis (AA+SS) groups. Colitis was induced by acetic acid. MoC extract, SS or saline were given to the related groups for 3 days. Interleukine-1β, malondialdehyde, glutathione levels, myeloperoxidase activity, bax/bcl-2 ratio, caspase-9 and caspase-3 levels were measured in colon and macroscopic and histopathologic examinations were done. Total phenolic/flavonoid content and biological activity of MoC were evaluated by in vitro analysis. Results: Compared to the control group, with acetic acid application interleukin-1β levels, myeloperoxidase activity, malondialdehyde levels, bax/bcl-2 ratio, caspase-9 and caspase-3 levels were significantly upregulated, while glutathione levels were significantly decreased in the AA group. In contrast, MoC and SS treatments reduced interleukin-1β, malondialdehyde levels, myeloperoxidase activity, bax/bcl-2 ratio, and caspase-9 and caspase-3 levels. Glutathione levels increased upon MoC or SS treatment. Increased macroscopic and microscopic scoring with AA improved with MoC or SS treatment, but the MoC or SS treated groups had higher score values than the control. Also, in vitro results showed that MoC exhibited 2,2-diphenyl-1picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activity as well as significant antilipoxygenase activity. In addition, MoC extract showed a potent anti-inflammatory activity compared to standard indomethacin. Conclusion: Our biochemical, in vitro and histopathologic analysis indicate that MoC is likely to prove beneficial in UC therapy.

Objective: This study aims to investigate the effect of Momordica charantia L. (MoC) ethanolic extract on ulcerative colitis (UC) and was explored in vitro and in vivo. Materials and Methods: The rats were divided into control (C), saline-treated colitis (AA), MoC extract-treated colitis (AA+MoC), and sulfasalazine (SS)-treated colitis (AA+SS) groups. Colitis was induced by acetic acid. MoC extract, SS or saline were given to the related groups for 3 days. Interleukine-1β, malondialdehyde, glutathione levels, myeloperoxidase activity, bax/bcl-2 ratio, caspase-9 and caspase-3 levels were measured in colon and macroscopic and histopathologic examinations were done. Total phenolic/flavonoid content and biological activity of MoC were evaluated by in vitro analysis. Results: Compared to the control group, with acetic acid application interleukin-1β levels, myeloperoxidase activity, malondialdehyde levels, bax/bcl-2 ratio, caspase-9 and caspase-3 levels were significantly upregulated, while glutathione levels were significantly decreased in the AA group. In contrast, MoC and SS treatments reduced interleukin-1β, malondialdehyde levels, myeloperoxidase activity, bax/bcl-2 ratio, and caspase-9 and caspase-3 levels. Glutathione levels increased upon MoC or SS treatment. Increased macroscopic and microscopic scoring with AA improved with MoC or SS treatment, but the MoC or SS treated groups had higher score values than the control. Also, in vitro results showed that MoC exhibited 2,2-diphenyl-1picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activity as well as significant antilipoxygenase activity. In addition, MoC extract showed a potent anti-inflammatory activity compared to standard indomethacin. Conclusion: Our biochemical, in vitro and histopathologic analysis indicate that MoC is likely to prove beneficial in UC therapy.

Objectives: To investigate the impact of exercise on ulcerogenesis. Materials and Methods: Gastric ulcer was induced in Wistar albino rats that were either kept sedentary or had swimming exercise for 6 weeks. Under anesthesia, ulcer was induced by applying acetic acid on the stomach serosa, while control rats had sham-operation. On 3rd or 10th days of ulcer induction, anxiety levels were measured and rats were decapitated for measuring serum cortisol level, while gastric tissue samples were obtained for histopathologic analysis and for determination of malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol-and lucigenin-enhanced chemiluminescence (CL) and nitric oxide (NO) levels. In sedentary 3-day-ulcer group, gastric MPO activities were elevated with concomitant reductions in GSH content, while these changes were reversed in 10-day ulcer group. In exercised 3-day-ulcer group, all parameters were significantly reversed. Increased lucigenin-CL was suppressed, while NO levels were elevated by exercise. Histological analysis revealed lower lesion scores in exercised groups. Serum cortisol levels were not different among ulcer groups, but anxiety was suppressed by swimming exercise in 3-day-ulcer group. Regular swimming exercise ameliorated acetic acid-induced oxidative damage of stomach via inhibition of neutrophil infiltration and through anti-stress effect of exercise. Regular exercise may be considered in facilitating the healing of gastric ulcers.

Background: Cisplatin-induced ototoxicity is related to oxidative stress. Astaxanthin is one of the most powerful antioxidants in nature. Aims/objectives: To investigate the protective effect of astaxanthin on cisplatin-induced ototoxicity. Materials and Methods: Thirty-five Sprague Dawley female rats were divided into 5 groups: control, cisplatin, and cisplatin with 10, 20, and 40 mg/kg astaxanthin groups. Cisplatin group received a single intraperitoneal injection of 14 mg/kg cisplatin. While saline was administered in the control group, in the other 3 groups, 10, 20, and 40 mg/kg daily doses of astaxanthin were administered through orogastric cannula before administration of cisplatin. Baseline and 10th day otoacoustic emission tests were administered. An intracardiac blood sample was taken to measure total antioxidant capacity (TAC), and the cochleas of the animals were investigated histopathologically. Results: Hearing level of astaxanthin 40 mg/kg + cisplatin group was higher ...

Amaç: Bu çalışmada, Beta glukan, fukoksantin ve kombinasyonlarının serulein kaynaklı akut pankreatit (AP) sıçan modelindeki etkileri araştırıldı. Gereç ve yöntem: Sıçanlar kontrol ve AP gruplarına ayrıldı. AP bir saat arayla dört kez serulein (20 ug/kg/ip) enjeksiyonuyla oluşturuldu. Serulein enjeksiyonundan 3 gün önce AP gruplarına günde 1 kez taşıyıcı, Beta glukan (BG;40 mg/kg/po), fukoksantin (Fuko;40 mg/kg/po) veya Beta glukan (BG;40 mg/kg/po) +fukoksantin (Fuko;40 mg/kg/po) uygulandı. Son enjeksiyondan sonraki 8. saatte ötenazi gerçekleştirildi. Serumda amilaz ve lipaz, pankreas dokusunda interlökin-1β (IL-1β), interlökin-6 (IL-6), interlökin-10 (IL-10), lucigenin kemilüminesans (CL), malondialdehit (MDA), miyeloperoksidaz (MPO) enzim aktivitesi ve Hematoksilen&Eosin (H&E), Siklooksijenaz-2 (COX-2), nükleer faktör kappa B (NF-κB) histopatolojik incelemeleri yapıldı. İstatistiksel analizler için tek yönlü ANOVA ve Bonferroni post-hoc testi uygulandı. Bulgular: Taşıyıcı grubunda;...

Methotrexate (MTX) is an effective cytotoxic agent which is used to treat malignancies and inflammatory diseases. Origanum onites (O. onites) is found throughout the Eastern Mediterranean region and has been used in traditional medicine. The essential oils (EOs) of O. onites rich in highly bioactive phytochemicals such as carvacrol (CVR) and has antiviral, antioxidant, anticancer and proapoptotic properties. The aim of this study was to investigate the protective effects of CVR and O. onites-EO treatment in MTX-induced hepatorenal toxic rats' liver and kidney tissues. The bcl-2/bax ratio, glutathione (GSH) level, malondialdehyde (MDA) level, and myeloperoxidase (MPO) activity of liver and kidney tissues were evaluated in the MTX-induced rat model. Results showed that the administration of CVR or O. onites-EO significantly increased bcl-2/bax expression and GSH levels as well as reduced MDA level and MPO activity in the kidney and liver tissues of MTX-induced rat model. In conclusion, our results suggest that O. onites-EO and CVR have protective effect in MTX-induced hepatorenal toxic rats' liver and kidney tissues by decreasing oxidative stress and apoptosis.