Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Hum Exp Toxicol. 2010 Aug;29(8):659-65. doi: 10.1177/0960327109359460. Epub 2010 Jan 11.
Carnosine is a dipeptide having strong antioxidant effects. Oxidative stress plays an important role in pathogenesis of alcohol-induced liver injury. In this study, we investigated the effect of carnosine pretreatment on ethanol-induced oxidative stress and hepatotoxicity. Rats were given carnosine (2 g/L in drinking water) for 4 weeks and then ethanol was administered orally to rats at a dose of 5 g/kg every 12 hours for 3 doses totally (binge model). All rats were killed 6 hours after last ethanol injection. Plasma alanine (ALT) and aspartate (AST) transaminase activities and liver triglyceride, malondialdehyde (MDA), diene conjugate (DC), glutathione (GSH), vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined. Binge ethanol administration resulted in significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. However, GSH, vitamin E, vitamin C levels and GSH-Px and GST activities were found to be decreased following ethanol administration. Macromicrovesicular steatosis was also seen. Carnosine pretreatment appeared to prevent the increase of plasma ALT and AST activities and hepatic MDA and DC levels following ethanol treatment. In addition, hepatic GSH levels increased, but there were no changes in triglyceride, vitamin E, vitamin C levels and SOD, GSH-Px and GST activities, following ethanol treatment in carnosine-pretreated rats. There was also no change in liver histopathological appearance. In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver.
肌肽是一种具有很强抗氧化作用的二肽。氧化应激在酒精性肝损伤的发病机制中起重要作用。在这项研究中，我们研究了肌肽预处理对乙醇诱导的氧化应激和肝毒性的影响。大鼠给予肌肽（饮用水中 2g/L）4 周，然后每隔 12 小时给予大鼠 5g/kg 乙醇，共 3 次（ binge 模型）。所有大鼠在最后一次乙醇注射后 6 小时处死。测定血浆丙氨酸（ALT）和天冬氨酸（AST）转氨酶活性以及肝甘油三酯、丙二醛（MDA）、二烯共轭物（DC）、谷胱甘肽（GSH）、维生素 E 和维生素 C 水平以及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和谷胱甘肽转移酶（GST）活性。 binge 乙醇给药导致血浆转氨酶活性、肝甘油三酯和脂质过氧化物水平显著增加。然而，给予乙醇后发现 GSH、维生素 E、维生素 C 水平以及 GSH-Px 和 GST 活性降低。还观察到巨微泡性脂肪变性。肌肽预处理似乎可防止乙醇处理后血浆 ALT 和 AST 活性以及肝 MDA 和 DC 水平的升高。此外，肝 GSH 水平增加，但肌肽预处理大鼠给予乙醇后甘油三酯、维生素 E、维生素 C 水平以及 SOD、GSH-Px 和 GST 活性无变化，肝组织病理学外观也无变化。总之，肌肽可防止乙醇处理大鼠血清转氨酶活性和肝脂质过氧化物的增加，而对肝脂肪变性无任何改变。
