Alcohol promotes liver fibrosis in high fat diet induced diabetic rats

Abstract Objectives Type 2 diabetes (T2DM) and alcoholism are considered to be lifestyle-associated independent risk factors in fatty liver diseases (FLD) mediated cirrhosis and hepatocellular carcinoma (HCC). A combined effect of both these conditions may exacerbate the pathological changes and a pre-clinical exploration of this is expected to provide a mechanical detail of the pathophysiology. The present study aims to understand the effect of alcohol on pre- diabetic and type 2 diabetic female Wistar rats. Methods In this experimental study, 12 Wistar rats (180–220 g) were randomly assigned into three groups: Normal (fed normal rat chow), alcohol (20 %) fed diabetic (HFD + STZ), and pre-diabetic rats (HFD alone). After, two months of the experimental period, blood and liver tissues were collected lipid metabolic alteration, liver injury, and fibrosis were determined following biochemical and histological methods. Data were analyzed using one-way ANOVA and Dunnett’s Post Hoc test. Results Significant dyslipidemia was observed in the liver tissues of diabetic and pre-diabetic rats following alcohol ingestion. A significant (p<0.05) increase in lipid peroxidation status, and hepatic marker enzyme activities (p<0.0001) were observed in diabetic animals. In corroborating with these observations, hematoxylin and eosin staining of hepatic tissue revealed the presence of sinusoidal dilation along with heavily damaged hepatocytes and inflammatory cell infiltration. Further, significantly (p<0.001) increased hepatic hydroxyproline content and extended picrosirius red stained areas of collagen in liver tissue indicated initiation of fibrosis in alcohol-fed diabetic rats. Conclusions Overall, the results indicate that alcohol consumption in T2DM conditions is more deleterious than pre diabetic conditions in progressing to hepatic fibrosis.