Cholestyramine Modulates Non-Alcoholic Steatohepatitis Induced by Methionine and Choline Deficiency in Rats: Cross-linking AGEs, MIP2, EMR1 and Adiponectin.

Abstract

The pathophysiological mechanisms underlying NASH mainly involve lipid accumulation and build-up in the hepatic tissues. Cholestyramine is a bile acid sequestrant commonly used for the treatment of hypercholesterolemia. Forty juvenile male albino Wistar rats were divided into four groups (n=10). The first group received a normal pellet diet for 2 months and served as the normal group. The remaining 3 groups received a Methionine and Choline-deficient diet (MCD) for 2 months to induce NASH. Group 2 was administered 0.5 ml distilled water and served as the NASH group. Groups 3 and 4 were administered oral cholestyramine (10 & 20 mg/kg; p.o.) for 2 months. MCD resulted in NASH as was manifested by significant alteration of hepatic histopathological pictures along with elevation of serum AST, ALT activities, serum TC, TG & LDL-cholesterol and a reduction in HDL-cholesterol levels. The liver weight and the liver index were also significantly elevated. Hepatic levels of AGEs, NF-kβ, TNF-α, MMP-9, MIP-2 & PPAR-γ along with iNOS & EMR1 gene expression were elevated while adiponectin level was reduced versus the normal group. Cholestyramine treatment (10 & 20 mg/kg) amended all the aforementioned parameters as compared to the NASH group. The current study is the first to identify cholestyramine's beneficial actions in NASH induced in rats by MCD. Furthermore, the study navigates the possible molecular mechanisms beyond cholestyramine's actions. cholestyramine treatment reduces hepatic fat accumulation as well as hepatic tissue inflammation.