Fucoidan, a sulfated polysaccharide extracted from various brown seaweeds, possesses a wide range of pharmacological properties. In this study, we investigated the protective effect of fucoidan on acetaminophen-induced acute liver injury in rats. Liver injury was induced by administration of acetaminophen (800 mg/kg, i.p.) and fucoidan was administered (100 mg kg, p.o.) 2 h before and after acetaminophen administration. After 24 h, co-treatment of fucoidan ameliorated liver damage and cell death induced by acetaminophen. Acetaminophen induced the overexpression of CYP2E1, one of the metabolizing enzymes of acetaminophen, but cotreatment with fucoidan suppressed its increased expression of CYP2E1. Fucoidan also reduced the hepatic apoptosis induced by acetaminophen exposure as shown in the protein expression of Bax, Bcl-2, and cleaved caspase-3. The anti-oxidative effect of fucoidan was observed from the increase of the production and expression of glutathione, superoxide dismutase, and glutathione peroxidase, both of which were decreased by acetaminophen. Also, fucoidan decreased the expression of inflammatory mediators, including tumor necrosis factoralpha, interleukin 1 beta, and inducible nitric oxide synthase. Taken together, the data demonstrate the hepato-protective effects of fucoidan against acetaminophen-induced liver injury via anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms.
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Angstwurm, K., Weber, J. R., Segert, A., Burger, W., Weih, M., Freyer, D., Einhaupl, K. M., and Dirnagl, U., Fucoidin, a polysaccharide inhibiting leukocyte rolling, attenuates inflammatory responses in experimental pneumococcal meningitis in rats. Neurosci. Lett., 191, 1–4 (1995)
Bajt, M. L., Farhood, A., Lemasters, J. J., and Jaeschke, H., Mitochondrial bax translocation accelerates DNA fragmentation and cell necrosis in a murine model of acetaminophen hepatotoxicity. J. Pharmacol. Exp. Ther., 324, 8–14 (2008)
Bilan, M. I., Grachev, A. A., Shashkov, A. S., Nifantiev, N. E., and Usov, A. I., Structure of a fucoidan from the brown seaweed Fucus serratus L. Carbohydr. Res., 341, 238–245 (2006).
Boyer, T. D. and Rouff, S. L., Acetaminophen-induced hepatic necrosis and renal failure. JAMA, 218, 440–441 (1971).
Dahlin, D. C., Miwa, G. T., Lu, A. Y., and Nelson, S. D., N-acetylp-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. Proc. Natl. Acad. Sci. U. S. A., 81, 1327–1331 (1984).
El-Hassan, H., Anwar, K., Macanas-Pirard, P., Crabtree, M., Chow, S. C., Johnson, V. L., Lee, P. C., Hinton, R. H., Price, S. C., and Kass, G. E., Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c, Bax, Bid, and caspases. Toxicol. Appl. Pharmacol., 191, 118–129 (2003).
Ferret, P. J., Hammoud, R., Tulliez, M., Tran, A., Trebeden, H., Jaffray, P., Malassagne, B., Calmus, Y., Weill, B., and Batteux, F., Detoxification of reactive oxygen species by a nonpeptidyl mimic of superoxide dismutase cures acetaminophen-induced acute liver failure in the mouse. Hepatology, 33, 1173–1180 (2001).
Hayashi, S., Itoh, A., Isoda, K., Kondoh, M., Kawase, M., and Yagi, K., Fucoidan partly prevents CCl4-induced liver fibrosis. Eur. J. Pharmacol., 580, 380–384 (2008).
Hierholzer, C., Harbrecht, B., Menezes, J. M., Kane, J., MacMicking, J., Nathan, C. F., Peitzman, A. B., Billiar, T. R., and Tweardy, D. J., Essential role of induced nitric oxide in the initiation of the inflammatory response after hemorrhagic shock. J. Exp. Med., 187, 917–928 (1998).
Hong, S. W., Jung, K. H., Lee, H. S., Zheng, H. M., Choi, M. J., Lee, C., and Hong, S. S., Suppression by fucoidan of liver fibrogenesis via the TGF-beta/Smad pathway in protecting against oxidative stress. Biosci. Biotechnol. Biochem., 75, 833–840 (2011).
Hu, T., Liu, D., Chen, Y., Wu, J., and Wang, S., Antioxidant activity of sulfated polysaccharide fractions extracted from Undaria pinnitafida in vitro. Int. J. Biol. Macromol., 46, 193–198 (2010).
Jaeschke, H., Reactive oxygen and mechanisms of inflammatory liver injury. J. Gastroenterol. Hepatol., 15, 718–724 (2000).
Jaeschke, H. and Lemasters, J. J., Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury. Gastroenterology, 125, 1246–1257 (2003).
Jollow, D. J., Thorgeirsson, S. S., Potter, W. Z., Hashimoto, M., and Mitchell, J. R., Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. Pharmacology, 12, 251–271 (1974).
Kang, K. S., Kim, I. D., Kwon, R. H., Lee, J. Y., Kang, J. S., and Ha, B. J., The effects of fucoidan extracts on CCl(4)-induced liver injury. Arch. Pharm. Res., 31, 622–627 (2008).
Li, B., Lu, F., Wei, X., and Zhao, R., Fucoidan: structure and bioactivity. Molecules, 13, 1671–1695 (2008).
Maruyama, H., Tamauchi, H., Hashimoto, M., and Nakano, T., Antitumor activity and immune response of Mekabu fucoidan extracted from Sporophyll of Undaria pinnatifida. In Vivo, 17, 245–249 (2003).
Masubuchi, Y., Suda, C., and Horie, T., Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice. J. Hepatol., 42, 110–116 (2005).
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., and Brodie, B. B., Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther., 187, 211–217 (1973).
Nakazato, K., Takada, H., Iha, M., and Nagamine, T., Attenuation of N-nitrosodiethylamine-induced liver fibrosis by high-molecular-weight fucoidan derived from Cladosiphon okamuranus. J. Gastroenterol. Hepatol., 25, 1692–1701 (2010).
Nelson, S. D., Mechanisms of the formation and disposition of reactive metabolites that can cause acute liver injury. Drug Metab. Rev., 27, 147–177 (1995).
Niehaus, W. G., Jr. and Samuelsson, B., Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur. J. Biochem., 6, 126–130 (1968).
Nishino, T., Nishioka, C., Ura, H., and Nagumo, T., Isolation and partial characterization of a novel amino sugar-containing fucan sulfate from commercial Fucus vesiculosus fucoidan. Carbohydr. Res., 255, 213–224 (1994).
Novo, E. and Parola, M., Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair, 1, 5 (2008).
Potter, W. Z., Davis, D. C., Mitchell, J. R., Jollow, D. J., Gillette, J. R., and Brodie, B. B., Acetaminophen-induced hepatic necrosis. 3. Cytochrome P-450-mediated covalent binding in vitro. J. Pharmacol. Exp. Ther., 187, 203–210 (1973).
Prescott, L. F., Kinetics and metabolism of paracetamol and phenacetin. Br. J. Clin. Pharmacol., 10 Suppl 2, 291S–298S (1980).
Rajkapoor, B., Venugopal, Y., Anbu, J., Harikrishnan, N., Gobinath, M., and Ravichandran, V., Protective effect of Phyllanthus polyphyllus on acetaminophen induced hepatotoxicity in rats. Pak. J. Pharm. Sci., 21, 57–62 (2008).
Tokita, Y., Nakajima, K., Mochida, H., Iha, M., and Nagamine, T., Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA. Biosci. Biotechnol. Biochem., 74, 350–357 (2010).
Vidali, M., Stewart, S. F., and Albano, E., Interplay between oxidative stress and immunity in the progression of alcohol-mediated liver injury. Trends Mol. Med., 14, 63–71 (2008)
Yan, S. L., Wu, S. T., Yin, M. C., Chen, H. T., and Chen, H. C., Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J. Food Sci., 74, H259–265 (2009).
Yang, J. W., Yoon, S. Y., Oh, S. J., Kim, S. K., and Kang, K. W., Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase. Biochem. Biophys. Res. Commun., 346, 345–350 (2006).
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Hong, SW., Lee, HS., Jung, K.H. et al. Protective effect of fucoidan against acetaminophen-induced liver injury. Arch. Pharm. Res. 35, 1099–1105 (2012). https://doi.org/10.1007/s12272-012-0618-5
- Liver injury