Novel Molecular Mechanism of Probiotics In Alcoholic Liver Disease

Abstract

Probiotics have been studied extensively for their potential role as an anti-inflammatory and anti-oxidant. The intestinal impermeability and increased translocation of gut flora through the gut liver axis to the liver possibly play a key role in alcoholic liver disease (ALD) progression. The alcohol affects expressions of tight junction (TJ) proteins. Alcohol even mediated generation of reactive oxygen species (ROS) results in systemic inflammation, inducing the polarisation of macrophages towards M1 i.e. pro-inflammatory type. Chronic alcohol uptake suppresses autophagy, which plays an important role in maintaining a cell s homeostasis. Since, ALD lacks Food and Drug Administration (FDA)-approved treatments, and molecular mechanism for the pathophysiological links between gut microbiota and the liver is unclear which is important for the development of new therapies to treat ALD. Recent studies suggest that some immunomodulatory probiotic bacteria show promising effects in inflammatory diseases. In this study, we tested the potential effect of probiotics for suppression of ALD through different cell lines and rat models and found out the possible molecular mechanism. newlineMethods: We have examined if probiotic V administration can prevent or reduce ethanol-induced damage in human liver cancer cells i.e. HepG2 cells, murine macrophage cell line i.e. RAW 264.7 cells, human colorectal adenocarcinoma cell line i.e. Caco-2 monolayers cells, and Wistar male rats. Markers of oxidative stress like ROS were assessed by 2and#8242;,7and#8242;-dichlorodihydrofluorescein diacetate (DCFDA) method and malondialdehyde (MDA) were assessed by high-performance liquid chromatography (HPLC) and thiobarbituric acid reactive substance (TBARS) assay along with nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase- 1 (HO-1), and newlinevii newlinecytochrome P450 Family 2 Subfamily E Member 1 (CYP2E1) gene expression. Serum levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglycerides, total cholesterol)