Sevgin Özlem İşeri

Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism.

UNLABELLED Oxytocin (OT), a nonapeptide produced in the paraventricular and the supraoptical nuclei in the hypothalamus has a wide range of effects in the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. OT may participate in the regulation of motility, secretion, blood flow, cell turnover and release of neurotransmitters and/or peptides in the GI tract, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in the modulation of immune and inflammatory processes. The present work was conducted to assess the possible therapeutic effects of OT against the acetic acid-induced colonic injury in the rat. METHODS Colitis was induced by intracolonic administration of acetic acid (5%) in Sprague-Dawley rats (200-250 g). Either saline or OT (0.5 mg/kg) was injected subcutaneously, immediately after the induction of colitis and repeated two times a day for 4 days. On the 4th day, rats were decapitated and distal 8 cm of the colon were removed for the macroscopic and microscopic damage scoring, determination of tissue wet weight index (WI), malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Colonic collagen content, as a fibrosis marker was also determined. Lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels were assayed in serum samples. In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p <0.05-<0.001). Treatment with OT abolished the colitis-induced elevations in damage scores, WI, MDA and MPO levels and restored the GSH levels (p <0.05-0.001). Similarly, acetic acid increased the collagen content of colonic tissues and OT-treatment reduced this value to the level of the control group. Serum LDH and TNF-alpha levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment. The results suggest that OT, which improves the antioxidative state of the colonic tissue and ameliorates oxidative colonic injury via a neutrophil-dependent mechanism, requires further investigation as a potential therapeutic agent in colonic inflammation.

Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats

BACKGROUND Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. OBJECTIVE The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). METHODS Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. RESULTS In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. CONCLUSION Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.

Oxytocin alleviates hepatic ischemia–reperfusion injury in rats

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.

The effect of sildenafil, a phosphodiesterase-5 inhibitor, on acetic acid-induced colonic inflammation in the rat

Background and Aim:  Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)‐dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant‐antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid‐induced colitis.

Oxytocin or Social Housing Alleviates Local Burn Injury in Rats

BACKGROUND Thermal injury may cause distant organ inflammation and multiorgan failure. Oxytocin (OT), a nonapeptide, modulates the immune and inflammatory processes. MATERIALS AND METHODS To investigate the effects of oxytocin on burn-induced tissue injury, Sprague-Dawley rats were subjected to a partial thickness burn. Immediately after burn, half of the burned rats were placed single in the cages, while others were caged in groups. All the rats then were treated with either OT (5 microg/kg, s.c) or saline twice daily for 5 d. The control rats had no burn injury and received no treatments. On day 5, the rats were decapitated, tissue and serum samples were obtained to score the severity of damage and to assay TNF-alpha levels. RESULTS Burn trauma resulted in oxidative ileal damage, as evidenced by increased apoptotic rate, increased neutrophil recruitment, and enhanced lipid peroxidation. OT treatment depressed the TNF-alpha level and alleviated dermal degeneration, while attenuating ileal damage. Although a higher degree of skin damage was observed in the animals kept isolated following burn injury, keeping the rats in groups did not affect the level of TNF-alpha or the severity of dermal or ileal injury, but abolished the burn-induced elevations in ileal lipid peroxidation and myeloperoxidase activity. Moreover, OT treatment reduced the ileal apoptosis when applied to rats housed in groups, while the treatment did not alter apoptotic ratio in the isolated rats. CONCLUSION Oxytocin can be considered as a potential agent in treating burn-induced distant organ injury.

Protective role of adrenomedullin in burn-induced remote organ damage in the rat

Clinical and experimental research findings suggest that a local burn insult produces oxidant-induced organ changes as evidenced by increased lipid peroxidation in lung, liver and gut. Adrenomedullin (AM), a potent vasodilator, was originally isolated from pheochromocytoma cells, and has been identified in other tissues. In this study, we investigated the potential role of AM in burn-induced remote organ damage in rats. Sprague-Dawley rats (250-300 g) were treated with either AM (100 ng/kg, subcutaneously) or saline 10 min before burn insult which covers 30% of total body surface area and were decapitated 24 h after the burn insult. Trunk blood was collected and analyzed for liver and kidney functions and for determination of TNF-alpha levels. The liver, lung and kidney samples were taken for histologic evaluation and for measurement of malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and chemiluminescence levels. The data revealed that AM treatment resulted in a significant protection in tissues tested against burn injury via suppression of lipid peroxidation, tissue neutrophil infiltration, oxidant generation and via decreasing circulating levels of the pro-inflammatory cytokine TNF-alpha. AM treatment was also effective in attenuating hepatic and kidney dysfunction due to burn injury, suggesting that peripherally AM administration may protect the tissues against burn-induced injury.