title: Vitamin C exerts beneficial hepatoprotection against Concanavalin A-induced immunological hepatic injury in mice through inhibition of NF-κB signal pathway.
abstract: The present study was designed to investigate the potential benefits of vitamin C (VC) in treating immunological liver injury induced by Concanavalin A (Con A, 20 mg kg(-1)) in mice. Interestingly, VC administration significantly reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total-bilirubin (T-bilirubin) in Con A-lesioned mice, while serum concentrations of albumin and total-protein (T-protein) were increased. Moreover, inflammatory cytokine profiles, such as interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8), were decreased in liver tissue by VC administration. Morphological examination showed that Con A-induced liver damage was effectively mitigated. As shown in RT-PCR assay, VC administration resulted in down-regulated mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, VC contributed towards the reduction of intrahepatic tumor necrosis factor alpha (TNF-α) and the receptor (TNF-R) protein levels, as well as decreasing IKKβ, p-IκBα, p50 and NF-κB expressions; furthermore, VC blocked intranuclear DNA-binding NF-κB locus. Our findings show that VC effectively attenuates Con A-mediated immunotoxicity in liver tissue, through an underlying mechanism which relates to dampening of the intrahepatic NF-κB signal pathway, thereby reducing cytotoxicity within hepatocytes.
authors.affiliation: College of Stomatology of Guangxi Medical University, Nanning 530021, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Chen
authors.forename: Guozhe
authors.initials: G
authors.lastname: Lu
authors.forename: Kun
authors.initials: K
authors.lastname: Liang
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003208:Concanavalin A / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D003208:Concanavalin A; D001205:Ascorbic Acid