“EZETIMIBE INHIBITS PROINFLAMMATORY MEDIATORS INVOLVED IN THE PATHOGENESIS OF NON ALCOHOLIC FATTY LIVER DISEASE”
a, Mohamed Ibrahim , a Entesar Farghaly, bWafaey Gomaa, a Mina Kelleni, aAly Abdelrahman
a Department of Pharmacology, Faculty of Medicine, Minia University.b Department of Pathology, Faculty of Medicine, Minia University.
Background and Purpose: non-alcoholic fatty liver disease (NAFLD) is a potentially progressive liver disease with multifactorial pathogenesis. There is no established drug therapy for NAFLD. This study investigated the effect of ezetimibe on multiple pathways involved in pathogenesis of NAFLD with special emphasis on the proinflammatory enzymes: induced nitric oxide synthase (iNOS) and Cyclooxygenase-2 (COX-2). Experimental approach: Experimental rats were assigned into 3 groups. Group 1 fed normal diet and served as normal control group. Group 2 fed 2% cholesterol diet and received vehicle as positive control NAFLD group. Group 3 fed 2% cholesterol diet plus ezetimibe. Rats were treated for eight weeks. Key results: ezetimibe prevented the development of NAFLD as evidenced by significant reduction in liver weight/body weight ratio (liver index) and confirmed by histopathological changes. The protective effect of ezetimibe was accompanied with significant decrease of hepatic tissue contents of triglycerides, lipid peroxidation product (malondialdehyde (MDA), nitric oxide (NO), and the proinflammatory enzymes: inducible nitric oxide syntahse (iNOS) and Cyclooxygenase-2 (COX-2).Conclusion: NAFLD has a multiple pathogenesis including increased hepatic tissue expression of iNOS and COX-2. Reduction of expression of iNOS and COX-2 in hepatic tissue participates in the protective effect of ezetimibe in NAFLD.