title: Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: studies on inflammation, oxidative stress, DNA damage and fibrosis.
abstract: Ulcerative colitis affects many people worldwide. Inflammation and oxidative stress play a vital role in its pathogenesis. Previously, we reported that ulcerative colitis leads to systemic genotoxicity in mice. The present study was aimed at elucidating the role of α-lipoic acid in ulcerative colitis-associated local and systemic damage in mice. Experimental colitis was induced using 3%w/v dextran sulfate sodium in drinking water for 2 cycles. α-Lipoic acid was administered in a co-treatment (20, 40, 80 mg/kg bw) and post-treatment (80 mg/kg bw) schedule. Various biochemical parameters, histological evaluation, comet and micronucleus assays, immunohistochemistry and western blot analysis were employed to evaluate the effect of α-lipoic acid in mice with ulcerative colitis. The protective effect of α-lipoic acid was mediated through the modulation of nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal transducer and activator of transcription 3, nuclear erythroid 2-related factor 2, NADPH: quinone oxidoreductase-1, matrix metalloproteinase-9 and connective tissue growth factor. Further, ulcerative colitis led to an increased gut permeability, plasma lipopolysaccharide level, systemic inflammation and genotoxicity in mice, which was reduced with α-lipoic acid treatment. The present study identifies the underlying mechanisms involved in α-lipoic acid-mediated protection against ulcerative colitis and the associated systemic damage in mice.
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India. priyankatrvd2@gmail.com
authors.forename: P P
authors.initials: PP
authors.lastname: Trivedi
authors.forename: G B
authors.initials: GB
authors.lastname: Jena
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001773:Blood Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D008070:Lipopolysaccharides / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D011897:Random Allocation; D008063:Thioctic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D019108:Tight Junctions / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008063:Thioctic Acid; D016264:Dextran Sulfate
keywords: % DNA; % DNA in comet tail; 3,3′-diaminobenzidinetetrahydrochloride; COX-2; CTGF; DAB; DAI; DMSO; DSS; EDTA; End-III; FPG; GSH; Genotoxicity; H&E; HBSS; Hank’s balanced salt solution; IL; Inflammation; LA; LMPA; LPS; MMP-9; MPO; NADPH: quinone oxidoreductase-1; NF-κB; NMPA; NQO-1; Nrf2; OTM; Oxidative stress; STAT3; TBARS; TL; TM; TNF-α; UC; Ulcerative colitis; VCAM-1; connective tissue growth factor; cyclooxygenase-2; dextran sulfate sodium; dimethylsulphoxide; disease activity index; endonuclease-III; ethylenediamine tetraacetic acid; formamidopyrimidine DNA glycosylase; hematoxylin and eosin; interleukin; lipopolysaccharide; low melting point agarose; matrix metalloproteinase-9; myeloperoxidase; normal melting point agarose; nuclear erythroid 2-related factor 2; nuclear factor-kappa B; olive tail moment; reduced glutathione; signal transducer and activator of transcription 3; tail length; tail moment; thiobarbituric acid-reactive substances; tumor necrosis factor-alpha; ulcerative colitis; vascular cell adhesion protein-1; α-Lipoic acid; α-lipoic acid