Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

AIM： To investigate the effects of resveratrol on liver ischemia/reperfusion （I/R） injury in rats. METHODS： A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups of ten： （1） controls： data from unmanipulated animals; （2） sham group： rats subjected to the surgical procedure, except for liver I/R, and given saline; （3） I/R group： rats underwent liver ischemia for 45 rain followed by reperfusion for 45 rain; （4） I-R/Resveratrol group： rats pretreated with resveratrol （10 umol/L, iv）. Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS： Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratroltreated livers. CONCLUSION： These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusionrelated liver injury.

Interaction of L-Arginine-methyl ester and Sonic hedgehog in liver ischemia-reperfusion injury in the rats

AIM： To investigate the role of Sonic hedgehog （Shh） on the course of liver ischemia and reperfusion （I/R） in rats, and the interaction between treatment with nitric oxide donor L-Arginine-methyl ester （L-Arg） and up-regulation of Shh expression.METHODS： A total of 30 male Sprague-Dawley rats weighing 220-240 g were used in this study. Shamcontrol group （G1, n = 10）： a sham operation was performed （except for liver I/R）. I/R-untreated group （G2, n = 10）： rats underwent liver ischemia for 1 h followed by reperfusion for 45 min. I/R-L-Arg group （G3, n = 10）： after performing the same surgical procedure as in group 2, animals were treated with L-Arg. Liver tissues were taken for determination of malondialdehyde （MDA） levels, and biochemical and histological evaluations were made.RESULTS： Plasma alanine aminotransferase （ALT）, aspartate aminotransferase （AS-T）, lactate dehydrogenase （LDH） and T-glutamyltranspeptidase （GGT） activities were higher in group 2 than in group 3. MDA values and the hepatic injury score decreased in the L-Arg treated group compared to the I/R-untreated group. In group 2, the hepatoo/tes were swollen with marked vacuolization. Group 3 rats showed well-preserved liver parenchyma, with hepatocytes extending from the central vein. The morphology of the hepatocytes and the sinusoidal structures was normal, without any signs of congestion. Mild Shh positive immunostaining was detected in group 2 animals. The expression of immunoreactive cells was increased markedly in liver tissue from I/R-L-Arg rats.CONCLUSION： Our findings suggest that Shh molecules are critical factors in the pathophysiology of inflammatory liver injury induced by I/R. In addition, NO plays an important role in the immunohistochemical expression of these molecules.

Dose-related effects of dexamethasone on liver damage due to bile duct ligation in rats

AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats, weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10) were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the two-week period, biochemical and histological evaluations were processed. RESULTS: The mean serum bilirubin and liver enzyme levels signifi cantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group. CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not signifi cantly lower in the high-dose corticosteroid group as compared to the low-dose group. Thus, low-dose corticosteroid provides asignifi cant reduction of liver damage without increased side effects, while high dose is associated not with lower fi brosis but with increased side effects.