Exploring Antioxidant and Anti-Inflammatory Responses in CCL4-Induced Liver Injury Mouse Model

Abstract

Liver injury is a major global health concern that is caused due to the damage of parenchymal and non-parenchymal cells of liver. It is characterized by oxidative stress and inflammation that accelerates to fibrosis, cirrhosis and hepatocellular carcinoma. In the liver injury major intracellular signaling pathways are activated. The inhibition of these pathways is a therapeutic target for treatment the of liver injury. Several studies have reported that juglone extracted from Reynoutria japonica has antioxidant, anti-inflammatory, anti-fibrotic and antidiabetic activity. In our study, we developed CCL4 liver injury mice model through multiple doses of 30% CCL4 on alternative days that mimics human liver injury pathogenesis. Hepatoprotective activity of juglone (5-hydroxy-1,4-naphthoquinones) and silymarin as a positive control was evaluated for hepatoprotection. Our compound treated group showed regain in the body weight and improved AST, ALT, and ALP profile in the serum. Histological analysis of liver confirms hepatoprotective activity of compound. Real time-PCR data shows overexpression of genes involved in inflammatory pathways, oxidative stress, liver fibrosis and cell death due to apoptosis. The genes were downregulated in compound treated group and silymarin group. Therefore, we concluded that our compound has hepatoprotective activity. Keywords: Liver injury, Oxidative Stress, Inflammation, Liver fibrosis, Juglone, CCL4