Adelmidrol protects against non-alcoholic steatohepatitis in mice.

Abstract

Non-alcoholic steatohepatitis (NASH) is a more serious condition of non-alcoholic fatty liver disease (NAFLD), a widely spread type of chronic liver disease. Oxidative stress and inflammation induced by lipotoxicity are involved in hepatic injury of NASH. This work aimed to investigate the possible protective effect of adelmidrol (PPAR α and γ agonist) against NASH in mice.Thirty-six mice were divided into six equal groups: sham-operated, NASH, vehicle, adelmidrol 5mg/kg, adelmidrol 10mg/kg, and adelmidrol 20mg /kg. Adelmidrol was injected intraperitoneally once daily for 7weeks along with high-fat diet (HFD). Mice were euthanized, and livers were removed for light microscopic examination and detection of reduced glutathione (GSH) content while blood samples were collected for assessment of transaminases (ALT& AST), tumor necrosis factor (TNF-α), matrix metalloproteinase-1 (MMP-1), adiponectin, cholesterol, high-density lipoprotein (HDL), and triglyceride. NASH mice had increments in MMP-1, TNF-α, AST, ALT, triglyceride, and cholesterol levels while HDL, adiponectin levels, and GSH content were decreased with vesicular steatosis, lobular inflammation, hepatocyte ballooning, and degeneration. Administration of adelmidrol decreased MMP-1, TNF-α, AST, ALT, triglyceride, and cholesterol levels while increased HDL, adiponectin levels, and GSH content as well as ameliorated the histopathological changes. Adelmidrol protected mice from NASH; an effect could be attributed to its anti-inflammatory and antioxidant actions.