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Abstract Nonalcoholic fatty liver disease (NAFLD) is recognize as the most common cause of chronic liver disease.Pro- and antiinflammatory cytokines play roles in the pathogenesis of NAFLD, oxidative stress and insulin resistance (IR). NAFLD is a condition of a ―two-hit‖process of pathogenesis since 1998 when Day and James first proposed this hypothesis. The first hit hepatic triglyceride accumulation, increases susceptibility of the liver to injury mediated by the second hits because of inflammatory cytokines/adipokines, oxidative stress and mitochondrial dysfunction, lead to steatohepatitis and fibrosis. A third-hit has been added to reflect inadequate hepatocyte proliferation. In the healthy liver, cell death stimulates replication of mature hepatocytes which replace dead cells and reconstitute normal tissue function. The aim of this work is to study the protective effect of Caffeine and curcumin versus silymarin on non alcholicsteatohepatitis induced by high fat high sucrose diet in rats. Fifty male albino rats, divided into five groups control group(A), group B receives high fat high sucrose diet (HFHS) for 16 weeks, group C receives high fat and high sucrose diet (HFHS) for 16 weeks and treated by silymerin at last 8 weeks, group D receives high fat high sucrose diet (HFHS) for 16 weeks and treated with curcumin at last 8 weeks and group E receives high fat high sucrose diet (HFHS) for 16 weeks and treated with caffiene at last 8 weeks. The following parameters were measured: Measurement of body weight and liver weight Laboratory investigations: measurement of serum glucose, insulin, Calculation of HOMA-IR, Cholesterol, measurement of hepatic triglycerides, TNFα, GSH and MDA. Histopathological examination: The liver slides that stained by hematoxylline & eosin also masson trichrome stain. HFHS group shows significance increase in body weight,liver weight ,serum glucose,serum insulin, HOMA-IR test ,total cholesterol, hepatic triglycerides,TNFα,GSH and MDA, compared to control group, silymerine, curcumin, caffiene treated group shows asignificant decrease in these parameters compared to HFHS group . As a conclusion results obtained from current study revealed that silymarin, curcumin and caffiene have a protective effect against NASH induced by HFHS diet in rats and revealed protection in histological finding and biochemical markers. Also there was no significant changes in biochemical results obtained from sylimarin treated, curcumin treated and caffiene treated groups. |