Fucoidan partly prevents CCl4-induced liver fibrosis

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown algae, has a wide range of biological activities, including anti-inflammatory, anti-viral, and anti-tumor activities. In the present study, we investigated the effects of fucoidan on CCl4-induced liver fibrosis. Administration of fucoidan reduced CCl4-induced acute and chronic liver failure. Hepatic fibrosis induced by CCl4 was also attenuated by injection of fucoidan. Damage to hepatocytes and activation of hepatic stellate cells are key events in liver fibrosis, and, interestingly, treatment of hepatocytes with fucoidan prevented CCl4-induced cell death and inhibited the proliferation hepatic stellate cells. These results indicate that fucoidan might be a promising anti-fibrotic agent possessing dual functions, namely, protection of hepatocytes and inhibition of hepatic stellate cell proliferation.

Fig. 1

Effect of fucoidan on CCl₄-induced hepatic injury. Mice received intraperitoneal injection of CCl₄ and intravenous injection of fucoidan. After 24 h, blood was recovered, and the serum AST (open column) and ALT (slashed column) levels were determined using commercially available kits. Results represent means ± S.D. (n = 4).

Fig. 2

Effect of fucoidan on CCl₄-induced chronic hepatic injury. Mice were injected orally with CCl₄ (0.3 ml/kg body weight) and intravenously with fucoidan (50 mg/kg body weight) twice a week for 8 weeks. (A) Blood was recovered for determination of serum AST (open column) and ALT (slashed column). Results indicate are means ± S.D. (n = 4). (B) Livers were recovered, sectioned, and stained with Azan. Blue and red areas correspond to fibrotic and normal regions, respectively. (C) The ratio of the fibrotic blue area to the blue and red area of the liver was calculated from the sections using NIH Scion Image. The calculation was performed on five images. Results represent means ± S.D. (n = 4).

Fig. 3

Effect of fucoidan on CCl₄-treated hepatocytes and hepatic stellate cells. (A) Effect of fucoidan on CCl₄-induced cell death in hepatocytes. Hepatocytes were treated with CCl₄ (1.0 mg/ml) in the absence or presence of fucoidan at the indicated concentration for 3 h. Viable cells were counted by Trypan blue staining. Results represent means ± S.D. (n = 4). (B) Effect of fucoidan on growth of hepatic stellate cells. Hepatic stellate cells were treated with fucoidan at the indicated concentration for 24 and 48 h. The viability of the cells was assayed by mitochondrial conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The growth ratio was calculated as a percentage of the viability at 0 h. Results represent means ± S.D. (n = 4).