کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2540297 | 1559755 | 2016 | 8 صفحه PDF | دانلود رایگان |
• Pretreatment of α-LA markedly attenuated Con A-induced hepatitis.
• α-LA reduces liver MDA and MPO levels and augments SOD and GSH levels.
• The mechanism relies on the inhibition of the phosphorylation of NF-κB p65, IκBα and JNK.
BackgroundAlpha-lipoic acid (α-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 α-LA against concanavalin A (Con A)-induced hepatitis in mice and explore the potential mechanism.MethodsAcute autoimmune hepatitis was induced by intravenous (IV) injection of Con A (15 mg/kg) in C57BL/6 mice. α-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-α, IL-6, IFN-γ 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-κB p65, IκBα and phosphorylated MAPK were measured by Western blot.ResultsCon A injection induced severe immune responses and extensive hepatocellular apoptosis within 12 h. Pretreatment of α-LA markedly reduced the serum ALT and AST activity and the increase of plasma TNF-α, IL-6, IFN-γ and IL-10. In addition, α-LA pretreatment decreased the tissue MPO activity and lipid peroxidation, but increased SOD and GSH levels. α-LA inhibited the phosphorylation of NF-κB p65, IκBα and JNK.ConclusionPretreatment of α-LA markedly attenuated Con A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation.
Journal: International Immunopharmacology - Volume 35, June 2016, Pages 53–60