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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.

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  • Authors+Show Affiliations

    ,

    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.

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    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.

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    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.

    ,

    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.

    ,

    Department of Rehabilitation and Physiotherapy, No. 324 Hospital of PLA, Chongqing 400020, People's Republic of China.

    ,

    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.

    ,

    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.

    ,

    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.

    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.

    Source

    International immunopharmacology 22:2 2014 Oct pg 293-302

    MeSH

    Alanine Transaminase
    Animals
    Anti-Inflammatory Agents
    Apoptosis
    Aspartate Aminotransferases
    Caspases
    Catalase
    Cytokines
    Galactosamine
    Glutathione Peroxidase
    Lipopolysaccharides
    Liver
    Liver Failure, Acute
    Male
    Mice
    NF-kappa B
    Nitric Oxide Synthase Type II
    Oxidative Stress
    Protective Agents
    Reactive Oxygen Species
    Thioctic Acid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25046589

    Citation

    Xia, Xiaomin, et al. "Role of Α-lipoic Acid in LPS/d-GalN Induced Fulminant Hepatic Failure in Mice: Studies On Oxidative Stress, Inflammation and Apoptosis." International Immunopharmacology, vol. 22, no. 2, 2014, pp. 293-302.
    Xia X, Su C, Fu J, et al. Role of α-lipoic acid in LPS/d-GalN induced fulminant hepatic failure in mice: studies on oxidative stress, inflammation and apoptosis. Int Immunopharmacol. 2014;22(2):293-302.
    Xia, X., Su, C., Fu, J., Zhang, P., Jiang, X., Xu, D., ... Song, Y. (2014). Role of α-lipoic acid in LPS/d-GalN induced fulminant hepatic failure in mice: studies on oxidative stress, inflammation and apoptosis. International Immunopharmacology, 22(2), pp. 293-302. doi:10.1016/j.intimp.2014.07.008.
    Xia X, et al. Role of Α-lipoic Acid in LPS/d-GalN Induced Fulminant Hepatic Failure in Mice: Studies On Oxidative Stress, Inflammation and Apoptosis. Int Immunopharmacol. 2014;22(2):293-302. PubMed PMID: 25046589.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Role of α-lipoic acid in LPS/d-GalN induced fulminant hepatic failure in mice: studies on oxidative stress, inflammation and apoptosis. AU - Xia,Xiaomin, AU - Su,Chuanyang, AU - Fu,Juanli, AU - Zhang,Pu, AU - Jiang,Xiaoji, AU - Xu,Demei, AU - Hu,Lihua, AU - Song,Erqun, AU - Song,Yang, Y1 - 2014/07/18/ PY - 2014/04/30/received PY - 2014/06/26/revised PY - 2014/07/08/accepted PY - 2014/7/22/entrez PY - 2014/7/22/pubmed PY - 2015/6/10/medline KW - Antioxidant KW - Apoptosis KW - Hepatoprotective KW - Inflammation KW - Lipopolysaccharide KW - d-Galactosamine SP - 293 EP - 302 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 22 IS - 2 N2 - 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. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/25046589/Role_of_α_lipoic_acid_in_LPS/d_GalN_induced_fulminant_hepatic_failure_in_mice:_studies_on_oxidative_stress_inflammation_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(14)00263-X DB - PRIME DP - Unbound Medicine ER -