Protective effects of L-carnosine on CCl4-induced hepatic injury in rats
Protective effects of L-carnosine on CCl4-induced hepatic injury in rats
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DOI：
10.1684/ecn.2016.0372
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发表时间：
2016-03-01
影响因子：
2.8
通讯作者：
El-Shishtawy, Mamdouh M.
中科院分区：
文献类型：
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作者：
Alsheblak, Mehyar Mohammad;Elsherbiny, Nehal M.;El-Shishtawy, Mamdouh M.
本研究旨在探讨 L-肌肽 (CAR)（一种丙氨酸和组氨酸的内源性二肽）对四氯化碳 (CCl4) 诱导的肝损伤的可能保护作用。通过腹膜内 (i.p.) 注射 CCl4 诱导雄性 Sprague-Dawley 大鼠肝损伤，每周两次，持续六周。每天给大鼠施用 CAR，剂量为 250 mg/kg，腹膜内注射。六周结束时，收集血液和肝组织标本。结果显示，肝脏组织病理学评分表明，CAR 治疗减轻了 CCl4 诱导的肝脏形态变化、坏死性炎症和纤维化。此外，CAR治疗显着降低了CCl4诱导的血清肝损伤参数升高。 CAR 治疗还可以对抗氧化应激；可能是通过恢复肝核因子红细胞 2 相关因子 2 (Nrf-2) 水平。此外，CAR治疗可防止肝星状细胞（HSC）的激活，肝脏中α-平滑肌肌动蛋白（α-SMA）表达减少，并减少肝脏炎症，肝肿瘤坏死因子-α（TNF-α）减少和白细胞介素10（IL-10）水平恢复。总之，CAR 治疗减轻了 CCl4 引起的肝损伤。结果表明，这些有益的保护作用至少部分归因于其抗氧化、抗炎和抗纤维化活性。
The present study was undertaken to investigate the possible protective effect of L-carnosine (CAR), an endogenous dipeptide of alanine and histidine, on carbon tetrachloride (CCl4)-induced hepatic injury. Liver injury was induced in male Sprague-Dawley rats by intraperitoneal (i.p.) injections of CCl4, twice weekly for six weeks. CAR was administered to rats daily, at dose of 250 mg/kg, i.p. At the end of six weeks, blood and liver tissue specimens were collected. Results show that CAR treatment attenuated the hepatic morphological changes, necroinflammation and fibrosis induced by CCl4, as indicated by hepatic histopathology scoring. In addition, CAR treatment significantly reduced the CCl4-induced elevation of liver-injury parameters in serum. CAR treatment also combated oxidative stress; possibly by restoring hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) levels. Moreover, CAR treatment prevented the activation of hepatic stellate cells (HSCs), as indicated by reduced alpha-smooth muscle actin (alpha-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-alpha (TNF-alpha) and restoration of interleukin-10 (IL-10) levels. In conclusion, CCl4-induced hepatic injury was alleviated by CAR treatment. The results suggest that these beneficial, protective effects are due, at least in part, to its anti-oxidant, anti-inflammatory and anti-fibrotic activities.