title: Alpha-lipoic acid protects mice against concanavalin A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation.
abstract: BACKGROUND
  Alpha-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.
  
  
  METHODS
  Acute autoimmune hepatitis was induced by intravenous (IV) injection of Con A (15mg/kg) in C57BL/6 mice. α-LA (100mg/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.
  
  
  RESULTS
  Con A injection induced severe immune responses and extensive hepatocellular apoptosis within 12h. 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.
  
  
  CONCLUSIONS
  Pretreatment of α-LA markedly attenuated Con A-induced hepatitis by modulating cytokine secretion and reducing reactive oxygen species generation.
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Fei
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Lulong
authors.initials: L
authors.lastname: Bo
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: lijinbaoshanghai@163.com.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: deng_x@yahoo.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D003208:Concanavalin A / Q000633:toxicity; D016207:Cytokines / Q000097:blood / Q000235:genetics; D018836:Inflammation Mediators / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D003208:Concanavalin A; D008063:Thioctic Acid; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Alpha-lipoic acid; Concanavalin A-induced hepatitis; Reactive oxygen species