Alsheblak Mehyar Mohammad, Elsherbiny Nehal M, El-Karef Amro, El-Shishtawy Mamdouh M
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Eur Cytokine Netw. 2016 Mar 1;27(1):6-15. doi: 10.1684/ecn.2016.0372.
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 combatted 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 α-smooth muscle actin (α-SMA) expression in the liver, and decreased hepatic inflammation as demonstrated by a reduction in hepatic tumor necrosis factor-α (TNF-α) 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.
本研究旨在探讨内源性二肽丙氨酸和组氨酸组成的L-肌肽（CAR）对四氯化碳（CCl4）诱导的肝损伤可能具有的保护作用。通过每周两次腹腔注射CCl4，连续六周，诱导雄性Sprague-Dawley大鼠肝损伤。以250mg/kg的剂量每天腹腔注射CAR给大鼠。六周结束时，采集血液和肝组织标本。结果表明，如肝脏组织病理学评分所示，CAR治疗减轻了CCl4诱导的肝脏形态学变化、坏死性炎症和纤维化。此外，CAR治疗显著降低了CCl4诱导的血清肝损伤参数升高。CAR治疗还对抗氧化应激；可能是通过恢复肝细胞核因子红细胞2相关因子2（Nrf-2）水平。此外，如肝脏中α平滑肌肌动蛋白（α-SMA）表达降低所示，CAR治疗可防止肝星状细胞（HSCs）激活，并且通过降低肝肿瘤坏死因子-α（TNF-α）和恢复白细胞介素-10（IL-10）水平证明可减轻肝脏炎症。总之，CAR治疗减轻了CCl4诱导的肝损伤。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。
