Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: Studies on inflammation, oxidative stress, DNA damage and fibrosis

• Published in: Food and chemical toxicology Vol. 59; pp. 339 - 355
• Main Authors: Trivedi, P.P., Jena, G.B.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2013; Elsevier
• Subjects: acid treatment; Animals; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biological and medical sciences; Blood Cells - drug effects; Blood Cells - immunology; Blood Cells - metabolism; Blood Cells - pathology; colitis; Colitis, Ulcerative - immunology; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Colitis, Ulcerative - prevention & control; Colon - drug effects; Colon - immunology; Colon - metabolism; Colon - pathology; dextran; Dextran Sulfate; digestive system; Disease Models, Animal; DNA damage; DNA Damage - drug effects; Dose-Response Relationship, Drug; drinking water; Fibrosis; Gastroenterology. Liver. Pancreas. Abdomen; gelatinase B; Genotoxicity; immunohistochemistry; Inflammation; Inflammation Mediators - blood; Inflammation Mediators - metabolism; interleukin-17; Intestinal Absorption - drug effects; lipoic acid; lipopolysaccharides; Lipopolysaccharides - blood; Lipopolysaccharides - metabolism; Male; Medical sciences; Mice; Micronuclei, Chromosome-Defective - drug effects; Organ Size - drug effects; Other diseases. Semiology; Oxidative stress; Oxidative Stress - drug effects; pathogenesis; people; permeability; Permeability - drug effects; prostaglandin synthase; protective effect; Random Allocation; signal transduction; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Thioctic Acid - administration & dosage; Thioctic Acid - therapeutic use; Tight Junctions - drug effects; Tight Junctions - immunology; Tight Junctions - metabolism; Tight Junctions - pathology; Toxicology; transcription factor NF-kappa B; Ulcerative colitis; Western blotting; α-Lipoic acid; α-Lipoic acid; Oxidative stress; COX-2; DMSO; Genotoxicity; OTM; MPO; UC; LPS; End-III; CTGF; NF-κB; LMPA; NMPA; Nrf2; GSH; NQO-1; IL; DAB; DSS; H&E; STAT3; TBARS; Inflammation; EDTA; DAI; VCAM-1; TNF-α; LA; DNA; TL; TM; HBSS; FPG; MMP-9; Ulcerative colitis; Lipoic acid; Toxicity; Rodentia; Inflammatory disease; Dextran; Vertebrata; Mammalia; Mouse; Blood substitute; Animal; Sodium sulfate; Fibrosis; Digestive diseases; Intestinal disease; Lesion; thiobarbituric acid-reactive substances; matrix metalloproteinase-9; cyclooxygenase-2; NADPH: quinone oxidoreductase-1; tumor necrosis factor-alpha; low melting point agarose; nuclear erythroid 2-related factor 2; normal melting point agarose; dextran sulfate sodium; nuclear factor-kappa B; DNA in comet tail; Hank’s balanced salt solution; connective tissue growth factor; lipopolysaccharide; ethylenediamine tetraacetic acid; formamidopyrimidine DNA glycosylase; dimethylsulphoxide; tail moment; reduced glutathione; interleukin; hematoxylin and eosin; 3,3′-diaminobenzidinetetrahydrochloride; olive tail moment; myeloperoxidase; signal transducer and activator of transcription 3; tail length; endonuclease-III; disease activity index; vascular cell adhesion protein-1
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.06.019

•α-Lipoic acid (LA) protected against ulcerative colitis (UC) in mice.•LA reduced inflammation, oxidative stress, DNA damage and fibrosis in mice with UC.•It prevented UC-induced increased gut permeability and reduced plasma LPS level.•It further reduced systemic inflammation and genotoxicity in mice with UC.•It ameliorated UC-induced local as well as systemic damage in mice. 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, 80mg/kg bw) and post-treatment (80mg/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.