title: Role of α-lipoic acid in LPS/d-GalN induced fulminant hepatic failure in mice: studies on oxidative stress, inflammation and apoptosis.
abstract: This study investigated the protective effect of α-lipoic acid (LA) on lipopolysaccharide (LPS)/d-galactosamine (d-GalN)-induced fulminant hepatic failure in mice. First, we found that LA markedly reduced LPS/d-GalN-induced increases in serum ALT and AST activities, which were supplemented with histopathological examination, suggested that LA has a protective effect on this model of hepatic damage. Livers challenged with LPS/d-GalN exhibited extensive areas of vacuolization with the disappearance of nuclei and the loss of hepatic architecture. On the contrary, these pathological alterations were ameliorated by LA treatment. Next, we found that ROS and TBARS levels were increased in LPS/d-GalN treated liver homogenates, which were attenuated by LA administration. Consistently, decreases in hepatic CAT and GPx activities were observed in LPS/d-GalN group and were significantly restored by LA administration. Moreover, pretreatment with LA markedly reduced LPS/d-GalN-induced iNOS, COX-2, TNF-α, NF-κB, IL-1β and IL-6 expressions. Furthermore, our data showed that TUNEL-positive cells increased in LPS/d-GalN-treated mice liver which was counteracted by LA administration. LPS/d-GalN induced apoptosis of hepatocytes, as estimated by caspase 3, caspase 8 and caspase 9 activations. Also, the increasing of Bax and the decreasing of Bcl-2 expressions also supported LPS/d-GalN induced apoptosis. Interestingly, LA marked relieved these apoptotic features. Taking together, our results indicated that LA plays an important role on LPS/d-GalN-induced fulminant hepatic failure through its antioxidant, anti-inflammatory and anti-apoptotic activities.
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Chuanyang
authors.initials: C
authors.lastname: Su
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Juanli
authors.initials: J
authors.lastname: Fu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation and Physiotherapy, No. 324 Hospital of PLA, Chongqing 400020, People's Republic of China.
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Demei
authors.initials: D
authors.lastname: Xu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China. Electronic address: eqsong@swu.edu.cn.
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China. Electronic address: songyangwenrong@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005688:Galactosamine; D005979:Glutathione Peroxidase / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D005688:Galactosamine; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020169:Caspases
keywords: Antioxidant; Apoptosis; Hepatoprotective; Inflammation; Lipopolysaccharide; d-Galactosamine