SITAGLIPTIN AMELIORATES ATORVASTATIN INDUCED HEPATOTOXICITY IN RATS

Abstract

Atorvastatin (ATOR) is the most widely used statin for the treatment of hypercholesterolemia, which is the most common cause of severe liver injury. Sitagliptin is a selective dipeptidyl peptidase-4 inhibitor (DPP4-I) used clinically as oral anti-diabetic agent. This study aimed to identify the effect of sitagliptin (SITA) pretreatment against Atorvastatin (ATOR) induced hepatotoxicity in albino rats. Twenty-five rats were divided into five groups (5 rats in each); normal control, ATOR, SITA and two sitagliptin groups, which pretreated with sitagliptin 10 and 20 mg/kg/day in combination with ATOR 20mg /kg / day for eight consecutive days prior to ATOR. The results revealed that ATOR induced noticeable hepatic injury in the form of moderate Hepatoportal + sinusoidal congestion, all Zonal changes, moderate Cloudy swelling + hydropic degeneration, moderate Fatty change and mild Apoptosis. Biochemical analysis exposed a significant rise in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in ATOR group. Increased Proinflammatory TNF-alpha, Oxidative stress MDA and depressed antioxidant system of GSH were evident in ATOR group. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological changes induced by ATOR. In conclusion, sitagliptin ameliorated the hepatotoxicity induced by atorvastatin. This effect was probably based through suppression of inflammatory, oxidative stress and apoptotic processes. Sitagliptin might exert beneficial effect on diabetic hepatic disorders which mandate further clinical research.