The anti-apoptotic effect of fucoxanthin on carbon tetrachloride-induced hepatotoxicity.
This study evaluated the anti-apoptotic activity of fucoxanthin in carbon tetrachloride (CCl(4))-induced hepatotoxicity. An in vitro study using the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay clearly demonstrated an attenuation of CCl(4)-induced hepatotoxicity with fucoxanthin. This effect was dose-dependent; 25 µM was more effective than 10 µM of fucoxanthin for attenuating the hepatotoxicity induced by 5 mM of CCl(4). Acute CCl(4)-hepatotoxicity in rats, with numerous cells positive for the terminal deoxynucleotidyl - transferase (TdT) -mediated deoxyuridine triphosphate-digoxigenin (dUTP) nick-end labeling (TUNEL) stain were seen in the pericentral area of the hepatic lobule. Oral pretreatment of CCl(4)- injected rats with fucoxanthin significantly reduced hepatocyte apoptosis. Fucoxanthin was immunohistochemically shown to increase heme oxygenase-1 expression in the cultured liver cells of Hc cells and TRL1215 cells. By oral pretreatment of CCl(4)-injected rats with fucoxanthin, the hepatic heme oxygenase-1 protein levels were significantly increased compared to those not pretreated with fucoxanthin. Heme oxygenase-1 mRNA expression after CCl(4 )injection was higher in the CCl(4)+fucoxanthin group than in the CCl(4 )group, although the difference was not significant. The findings suggest that fucoxanthin attenuates hepatocyte apoptosis through heme oxygenase-1 induction in CCl(4)-induced acute liver injury.
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Mieko
M
Kaneko
Takeaki
T
Nagamine
Kyoumi
K
Nakazato
Masatomo
M
Mori
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D024341:Xanthophylls / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C491055:Mt2A protein, rat; D020011:Protective Agents; D024341:Xanthophylls; C025164:fucoxanthin; D008668:Metallothionein; D002251:Carbon Tetrachloride; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase