Alpha-lipoic acid protects mice against concanavalin A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation

Background: Alpha-lipoic acid (alpha-LA), which exits in almost all types of prokaryotic and eukaryotic cells, is a key regulator of energy metabolism in mitochondria. This study was designed to explore the protective effect of alpha-LA against concanavalin A (Con A)-induced hepatitis in mice and explore the potential mechanism. Methods: Acute autoimmune hepatitis was induced by intravenous (IV) injection of Con A (15 mg/kg) in C57BL/6 mice. alpha-LA (100 mg/kg) was administered four days before Con A injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and histopathological change of the liver tissue were measured. Serum cytokine TNF-alpha, IL-6, IFN-gamma and IL-10 were detected by ELISA. The mRNA levels of these inflammatory cytokines in the liver were detected by RT-PCR. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and reduced/oxidized glutathione (GSH/GSSG) in liver were determined using commercial kits. Phosphorylated NF-kappa B p65, I kappa B alpha and phosphorylated MAPK were measured by Western blot. Results: Con A injection induced severe immune responses and extensive hepatocellular apoptosis within 12 h. Pretreatment of alpha-LA markedly reduced the serum ALT and AST activity and the increase of plasma TNF-alpha, IL-6, IFN-gamma and IL-10. In addition, alpha-LA pretreatment decreased the tissue MPO activity and lipid peroxidation, but increased SOD and GSH levels. alpha-LA inhibited the phosphorylation of NF-kappa B p65, I kappa B alpha and JNK. Conclusion: Pretreatment of alpha-LA markedly attenuated Con A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation. (C) 2016 Elsevier B.V. All rights reserved.