Protective effects of green tea polyphenols against subacute hepatotoxicity induced by microcystin-LR in mice.
Protective effects of green tea polyphenols against subacute hepatotoxicity induced by microcystin-LR in mice.
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DOI：
10.1016/j.etap.2007.04.004
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发表时间：
2007-09
影响因子：
4.3
通讯作者：
Chuan Xu;W. Shu;Z. Qiu;Ji-An Chen;Qing-Ning Zhao;Jia Cao
中科院分区：
文献类型：
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作者：
Chuan Xu;W. Shu;Z. Qiu;Ji-An Chen;Qing-Ning Zhao;Jia Cao
绿色茶多酚（GTP）具有抗氧化、抗突变和抗致癌活性。本研究旨在评价GTP对微囊藻毒素-LR（MC-LR）诱导的小鼠亚急性肝毒性的化学预防作用，并探讨其机制。本实验选用健康昆明种雄性小鼠（24- 26 gbw），随机分为5组。I组喂普通饲料，自由饮水作为对照。Ⅱ组从第6天开始腹腔注射MC-LR（10μg/kg/d），直至处死。在第III、IV和V组中，从MC-LR中毒前第0天开始，每天通过灌胃给予50、100和200 mg/kg/天的GTP，连续18天。结果表明，MC-LR单独使用可导致氧化应激和抗氧化防御系统受损，表现为血清和肝脏脂质过氧化水平升高。此外，还观察到肝细胞凋亡和损伤。GTP预处理可显著提高血清抗氧化酶GSH和SOD活性，降低肝脏脂质过氧化产物MDA水平和血清ALT、AST、ALP活性。GTP预处理明显抑制肝细胞凋亡，上调Bcl-2蛋白表达。GTP预处理组小鼠肝脏损伤较轻，且与生化指标相关。总之，本研究证实了重复暴露于MC-LR可诱导肝毒性。我们的研究表明，GTP可以降低MC-LR诱导的氧化应激，并以剂量依赖性的方式防止MC-LR引起的生化参数和病理变化。结果表明，茶多酚有潜力被开发作为一种预防剂对MC-LR诱导的毒性和参与的保护机制可能是由于其抗氧化活性。
Green tea polyphenols (GTP) have been shown to possess anti-oxidative, anti-mutagenic and anti-carcinogenic activities. The present study aimed to evaluate the chemopreventive efficacy of GTP against subacute hepatotoxicity induced by microcystin-LR (MC-LR) in mice and also elucidates the underlying mechanisms. In this study, healthy Kunming male mice (24–26gbw) were randomly assigned to five groups. Group I was fed on normal diet and water ad libitum as control. Group II was maintained on normal diet and received MC-LR intraperitoneal injection (10μg/kg/day) from day 6 till sacrifice. Mice in groups III, IV and V were daily pre-treated with GTP through intragastric administration at doses of 50, 100 and 200mg/kg/day from day 0 prior to MC-LR intoxication, consecutively 18 days. The results showed MC-LR alone led to oxidative stress and to damage antioxidant defense system, as evidenced by elevation of serum and liver lipid peroxidation. Additionally, hepatocellular apoptosis and injury were significantly observed. GTP pre-treatment caused a significant elevation in serum antioxidant enzymes GSH and SOD activities as well as a decrease in hepatic lipid peroxidation MDA level and serum ALT, AST, ALP activities. GTP pre-treatment obviously inhibited hepatocellular apoptosis and up-regulated Bcl-2 protein expression. The damages in liver were less severe in GTP pre-treated mice in correlation with the biochemical parameters. In summary, this study confirmed that repeated exposure to MC-LR could induce hepatotoxicity. Our study demonstrated that GTP can reduce MC-LR-induced oxidant stress and prevent biochemical parameters and pathological changes caused by MC-LR in a dose-dependent manner. The results indicated that tea polyphenols have a potential to be developed as a preventive agent against MC-LR-induced toxicity and the mechanism involved in the protection could be due to their antioxidant activities.