鼠尾草酸对大鼠的急性经口毒性及其机制

The acute oral toxicity and the toxic mechanism of carnosic acid in Sprague-Dawley rats

目的测定鼠尾草酸(carnosic acid,CA)经口灌胃Sprague-Dawley(SD)大鼠的半数致死量(LD_(50)),并探讨引起动物急性死亡的可能机制。方法取SD大鼠50只,雌雄各半,采用霍恩氏法随机分组,经口染毒,观察14 d,计算其LD_(50),并对主要脏器进行病理学检查。另取SD大鼠40只,雌雄各半,随机分组,以LD_(50)剂量的CA一次性经口染毒后,分别于0、1、4、8 h采血,检测血清中肝肾功能指标、总超氧化歧化酶(total superoxide dismutase,T-SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-PX)、丙二醛(malondialdehyde,MDA)和α肿瘤坏死因子(tumor necrosis factor-α,TNF-α)的含量;同时处死动物取肝和肺制成组织匀浆测定T-SOD、GSH-PX、MDA含量。结果 CA对雄雌SD大鼠的急性经口LD_(50)为3.16 g·kg^(-1)(95%可信限为1.86～5.38 g·kg^(-1))。光镜下死亡动物肝、肾和肺组织可见明显病理学改变;以3.16 g·kg^(-1)剂量的CA一次性经口染毒后,SD大鼠血清中谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、尿素氮(blood urine nitrogen,BUN)、肌酐(creatinine,Cr)的水平,以及肝组织中T-SOD和肺组织中GSH-PX和MDA含量随时间而发生了显著变化。结论 CA属低毒,其急性毒性损伤的主要器官为肝、肾和肺。

Objective To observe the acute oral toxicity of carnosic acid （CA） in Sprague-Dawley （SD） rats and calculate its 50% lethal dose （LD50）, then inquire into its toxic mechanism. Methods Horn＇s method was adopted. Fifty SD rats of both sexes were randomized and orally administered with CA at doses of 0, 1.00, 2. 15,4. 64, 10. 00 g·kg-1 respectively. After observing the symptoms and death of the rats for 14 d, LD50 was evaluated by Horn＇s table. The pathological examination of major organs was conducted. Further, 40 SD rats of both sexes were randomly divided into four groups according to the time of 0, 1,4, 8 h after CA was orally administered at the dose of LD50 once. Hepatic and renal functions were evaluated by bio- chemical assays. The levels of total superoxide dismutase （ T-SOD ）, glutathione peroxidase （ GSH-PX）, malondialdehyde （MDA） and tumor necrosis factor-a（TNF-a） in serum were measured to evaluate injures. Finally, the rats were euthanized and the levels of T-SOD, GSH-PX and MDA were analyzed by the meth- od of spectrophotometry. Results The acute oral LD50 value of CA for male and female SD rats was 3.16 g·kg-1 （95% confidence interval, 1.86-5.38 g·kg-1 ）. The livers, kidneys and lungs of the dead rats showed obvious pathological changes. Levels of alanine aminotransferase（ ALT）, aspartate aminotrans- ferase （AST）, creatinine （Cr）, blood urine nitrogen（BUN） in serum had significantly fluctuated with time. Meanwhile the levels of T-SOD in livers and GSH-PX in lungs significantly decreased. On the other hand, the levels of MDA in lungs significantly increased after the SD rats were orally administered with CA at dose of 3. 16 g·kg-1. Conclusions CA is determined as a low toxic substance. A large amount of CA will do harm to livers, kidneys and lungs of SD rats.