Department of Biomedical Sciences and NCEED, School of Medicine, Inha University, Incheon 400-712, Korea.
Arch Pharm Res. 2012 Jun;35(6):1099-105. doi: 10.1007/s12272-012-0618-5. Epub 2012 Jun 30.
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.
岩藻聚糖硫酸酯是从各种褐藻中提取的一种硫酸多糖,具有广泛的药理作用。本研究探讨了岩藻聚糖硫酸酯对乙酰氨基酚诱导的大鼠急性肝损伤的保护作用。采用乙酰氨基酚(800mg/kg,腹腔注射)诱导肝损伤,岩藻聚糖硫酸酯(100mg/kg,灌胃)在乙酰氨基酚给药前 2 小时和后 2 小时给药。24 小时后,岩藻聚糖硫酸酯联合治疗改善了乙酰氨基酚引起的肝损伤和细胞死亡。乙酰氨基酚诱导细胞色素 P450 2E1(乙酰氨基酚的代谢酶之一)的过度表达,但岩藻聚糖硫酸酯联合治疗抑制了其表达的增加。岩藻聚糖硫酸酯还降低了乙酰氨基酚暴露引起的肝凋亡,表现为 Bax、Bcl-2 和 cleaved caspase-3 蛋白表达降低。岩藻聚糖硫酸酯的抗氧化作用表现为谷胱甘肽、超氧化物歧化酶和谷胱甘肽过氧化物酶的产生和表达增加,而乙酰氨基酚则降低了它们的表达。此外,岩藻聚糖硫酸酯还降低了肿瘤坏死因子-α、白细胞介素 1β和诱导型一氧化氮合酶等炎症介质的表达。综上所述,数据表明岩藻聚糖硫酸酯通过抗氧化、抗炎和抗凋亡机制对乙酰氨基酚诱导的肝损伤具有保护作用。