Alcohol exacerbated biochemical and biophysical alterations in liver mitochondrial membrane of diabetic male wistar rats – A possible amelioration by green tea

Abstract

Summary: Objectives: The biological membranes are important for cell structure and function but, during diseased conditions such as diabetes and in chronic alcoholism, they may be impaired. Nitroxidative stress mediated by persistent hyperglycemia is a major complication in diabetics with alcohol abuse. The present study is intended to investigate the antioxidant, anti-diabetic, and hepatoprotective effects of aqueous green tea extract (GTE) against cumulative effects of alcohol and diabetic pathology, focusing liver mitochondrial membranes. Methods: Mitochondrial membrane fluidity and membrane Na+/K+ and Mg2+ATPases were measured. Displacement loop (D-loop) of mitochondrial DNA (mt-DNA) was screened by PCR-Sanger's sequencing method. In addition, nuclear and mitochondrial encoded genes were analyzed. Molecular docking studies were performed to screen potential targets using the docking module implemented in Pyrx2010. Results: In the present study, marked mitochondrial-DNA deletions were observed in diabetic-alcohol group which were ameliorated by GTE treatment. Also, GTE restored the alterations in the exacerbated levels of membrane fluidity and activities of Na+/K+ and Mg2+ ATPase to normalcy. ADME properties were evaluated for the ligand, Epigallocatechin 3 Gallate (EGCG) and reference drug, Rosiglitazone (RTG). It showed that, higher binding affinities and energy profiles of EGCG with the active site ofinducible nitric oxide synthase (iNOS) compared to RTG making non-bonded interactions with their active residues and surrounding allosteric residues. Discussion: The present investigation demonstrated that, EGCG would be a promising next generation anti-diabetic compound as well as anti-inflammatory drug, and may be effectively used in the treatment of hepatopathy induced by double jeopardy of diabetes and alcohol abuse.

Keywords

• Diabetes
• Alcohol
• Hepatic dysfunction
• Mt-DNA D-loop
• Green tea