Protection by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) against the hepatotoxicity of aflatoxin B1 in the rat.
Protection by 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) against the hepatotoxicity of aflatoxin B1 in the rat.
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5-(2-吡嗪基)-4-甲基-1,2-二硫醇-3-硫酮 (oltipraz) 对大鼠黄曲霉毒素 B1 的肝毒性具有保护作用。
DOI：
10.1016/0041-008x(88)90047-6
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发表时间：
1988
影响因子：
3.8
通讯作者：
Kensler,TW
中科院分区：
文献类型：
--
作者：
Liu,YL;Roebuck,BD;Yager,JD;Groopman,JD;Kensler,TW
评价了一种新的化学保护剂奥替拉兹对黄曲霉毒素B1所致的肝毒性的缓解作用。雄性F344大鼠喂食添加0.075%奥替拉兹的饲料，并与只喂纯净饲料(AIN)的大鼠进行比较。在黄曲霉毒素B1(AFB1)治疗前和整个实验期内，给大鼠喂饲这些饲料1周。黄曲霉毒素B_1以0.25~10 mg/kg体重单次灌胃给药，用于急性毒性研究；以0.25 mg/kg/kg多次灌胃，5天/周，共2周，用于亚慢性毒性研究。后一种方案构成了致瘤剂量方案。在一项急性毒性研究中，奥替普拉预处理将10毫克/公斤黄曲霉毒素1的死亡率从83%降低到36%。奥替普拉兹显著抑制亚致死剂量黄曲霉毒素B_1引起的血清丙氨酸氨基转移酶和山梨醇脱氢酶水平升高。在亚慢性毒性研究中，喂食AIN饮食的AFB1处理的大鼠在2周的治疗期内未能增加体重，它们的肝脏重量严重下降。相比之下，在AFB1治疗期间，喂食奥替拉兹的大鼠保持了较高的生长速度。亚慢性AFB1治疗方案也导致肝脏中超过75%的预先标记的[~3H]胸腺嘧啶核苷丢失，而补充奥替拉兹在很大程度上阻止了这种损失。综上所述，上述结果表明奥替拉兹对黄曲霉毒素B_1的毒性作用有明显的改善作用。
A new chemoprotective agent, oltipraz, was evaluated for alleviation of aflatoxin B1-induced hepatotoxicity. Male F344 rats were fed a diet supplemented with 0.075% oltipraz and compared to rats fed the purified diet (AIN) alone. Rats were fed these diets for 1 week prior to treatment with aflatoxin B1(AFB1) and throughout the experimental period. AFB1was administered to rats by gavage in single doses ranging from 0.25 to 10 mg/kg body weight for acute toxicity studies and in multiple doses of 0.25 mg/kg, 5 days/week, for 2 weeks for subchronic toxicity studies. The latter protocol constitutes a tumorigenic dosing regimen. In an acute toxicity study, pretreatment with oltipraz reduced from 83 to 36% the mortality produced by 10 mg/kg AFB1. Oltipraz significantly suppressed the elevated serum levels of alanine amino transaminase and sorbitol dehydrogenase induced by sublethal doses of AFB1. In subchronic toxicity studies, the AFB1-treated rats fed AIN diet failed to gain weight over the 2-week treatment period and their liver weights were severely depressed. In contrast, the rats fed the oltipraz supplemented diet maintained a high rate of growth during AFB1treatment. The subchronic AFB1treatment regimen also resulted in over 75% loss of prelabeled [3H]thymidine from the liver while oltipraz supplementation largely prevented this loss. Taken together, these results indicate that oltipraz is very effective in ameliorating the toxic effects of AFB1in rats.