Abstract
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. (C) 2011 Elsevier B.V. All rights reserved.