title: The molecular mechanisms of the hepatoprotective effect of gomisin A against oxidative stress and inflammatory response in rats with carbon tetrachloride-induced acute liver injury.
abstract: Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl(4))-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl(4) markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatment ameliorated mRNA levels of CCl(4)-induced inflammatory mediators, including tumor necrosis factor-α, interleukin-1β and inducible nitric oxide (NO) synthase, and the protein levels of transcriptional upregulator nuclear factor kappa B (NF-κB) and phospho-inhibitor of NF-κB (IκB). Furthermore, α-smooth muscle actin (α-SMA), a myofibroblast marker, was also inhibited by gomisin A treatment. These results suggest that gomisin A inhibits the oxidative stress and activation of NF-κB, leading to down-regulation of pro-inflammatory mediators and amelioration of fibrogenesis.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Graduate School of Musashino University, Tokyo, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Teraoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.forename: Masaki
authors.initials: M
authors.lastname: Aburada
mesh_terms: D000199:Actins / Q000235:genetics; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology / Q000627:therapeutic use*; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000235:genetics; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002251:Carbon Tetrachloride; D034242:Cyclooctanes; D004149:Dioxoles; D053583:Interleukin-1beta; D017705:Lignans; D008315:Malondialdehyde; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D020011:Protective Agents; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat; C033585:schizandrol B; C496318:Nos2 protein, rat