This study evaluated the anti-apoptotic activity of fucoxanthin in carbon tetrachloride (CCl4)-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 CCl4-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 CCl4. Acute CCl4-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 CCl4- 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 CCl4-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 CCl4 injection was higher in the CCl4+fucoxanthin group than in the CCl4 group, although the difference was not significant. The findings suggest that fucoxanthin attenuates hepatocyte apoptosis through heme oxygenase-1 induction in CCl4-induced acute liver injury.
2013 The Japanese Society of Toxicology