Fourteen-Week Toxicity Study of Green Tea Extract in Rats and Mice

Fourteen-Week Toxicity Study of Green Tea Extract in Rats and Mice
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DOI:
10.1177/0192623310382437
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发表时间:
2010-12-01
影响因子:
1.5
通讯作者:
Nyska, Abraham
Nyska, Abraham
中科院分区:
医学4区
文献类型:
--
作者:
Chan, Po C.;Ramot, Yuval;Nyska, Abraham

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在雄性和雌性F344/NTac大鼠和B6 C3 F1小鼠的14周灌胃研究中,以高达1,000 mg/kg的剂量评价了绿色茶提取物(GTE)的毒性。在大鼠中,未观察到给药相关死亡。在小鼠中,1,000 mg/kg剂量组的雄性和雌性小鼠发生给药相关死亡。早期死亡的原因可能与肝坏死有关。在两个种属的肝脏、鼻、肠系膜淋巴结和胸腺中观察到给药相关组织病理学变化。此外,在小鼠中,在派伊尔集合淋巴结、脾脏和下颌淋巴结中观察到变化。两个物种肝脏的无不良作用水平(NOAEL)均为500 mg/kg。在大鼠鼻中,雄性的NOAEL为62.5 mg/kg,雌性未发现NOAEL,雌性和雄性小鼠鼻中均未发现NOAEL。肝脏和鼻的变化被认为是GTE的主要毒性作用,而其他器官的变化被认为是次要作用。鼻子和肝脏是具有高代谢酶活性的器官。鼻和肝脏的易感性增加表明GTE代谢物在毒性诱导中的作用。
The toxicity of green tea extract (GTE) was evaluated in 14-week gavage studies in male and female F344/NTac rats and B6C3F1 mice at doses up to 1,000 mg/kg. In the rats, no treatment-related mortality was noted. In the mice, treatment-related mortality occurred in male and female mice in the 1,000 mg/kg dose groups. The cause of early deaths was likely related to liver necrosis. Treatment-related histopathological changes were seen in both species in the liver, nose, mesenteric lymph nodes, and thymus. In addition, in mice, changes were seen in the Peyer's patches, spleen, and mandibular lymph nodes. The no adverse effect level (NOAEL) for the liver in both species was 500 mg/kg. In the nose of rats, the NOAEL in males was 62.5 mg/kg, and in females no NOAEL was found. No NOAEL was found in the nose of female or male mice. The changes in the liver and nose were considered primary toxic effects of GTE, while the changes in other organs were considered to be secondary effects. The nose and liver are organs with high metabolic enzyme activity. The increased susceptibility of the nose and liver suggests a role for GTE metabolites in toxicity induction.