Department of Pharmacology, Faculty of Medicine, Minia University, Egypt.
Eur J Pharmacol. 2011 Jun 1;659(2-3):289-95. doi: 10.1016/j.ejphar.2011.03.016. Epub 2011 Mar 29.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury; however its therapeutic strategy has not been established yet. Nitro-aspirin (NO-aspirin) is a new molecule in which aspirin and a NO-donating group are covalently linked. This study investigated the potential protective effect of NO-aspirin on NAFLD. Experimental rats were assigned into 4 groups. Group 1 was fed with normal diet and served as normal control group. Group 2 was fed with 2% cholesterol diet and received vehicle as positive control NAFLD group. Group 3 was fed with 2% cholesterol diet plus NO-aspirin (100 mg/kg/day). Group 4 was fed with 2% cholesterol diet plus aspirin (55 mg/kg/day). Rats were treated for 8 weeks. The results showed that NO-aspirin (but not aspirin) prevented the development of NAFLD as evidenced by significant reduction in liver weight/body weight ratio (liver index) and histopathologic changes. The protective effect of NO-aspirin is accompanied with significant decrease in triglycerides, malondialdehyde (MDA), and nitric oxide (NO) in hepatic tissue. Semi-quantitative immunohistochemical studies showed significant decrease in expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in hepatic tissue. In conclusion, NO-aspirin inhibited multiple pathways involved in the pathogenesis of NAFLD indicating that it might serve as a new therapeutic strategy.
非酒精性脂肪性肝病(NAFLD)是慢性肝损伤的最常见原因;然而,其治疗策略尚未确定。硝基阿司匹林(NO-aspirin)是一种新的分子,其中阿司匹林和一个 NO 供体基团通过共价键连接。本研究探讨了 NO-aspirin 对 NAFLD 的潜在保护作用。实验大鼠被分为 4 组。第 1 组给予正常饮食,作为正常对照组。第 2 组给予 2%胆固醇饮食,并给予载体作为阳性对照 NAFLD 组。第 3 组给予 2%胆固醇饮食加 NO-aspirin(100mg/kg/天)。第 4 组给予 2%胆固醇饮食加阿司匹林(55mg/kg/天)。大鼠治疗 8 周。结果表明,NO-aspirin(而不是阿司匹林)可预防 NAFLD 的发生,肝重/体重比(肝指数)和组织病理学变化明显降低。NO-aspirin 的保护作用伴随着肝组织中甘油三酯、丙二醛(MDA)和一氧化氮(NO)的显著减少。半定量免疫组织化学研究表明肝组织中诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达显著降低。总之,NO-aspirin 抑制了 NAFLD 发病机制中涉及的多个途径,表明它可能成为一种新的治疗策略。