Preetha S P, Kanniappan M, Selvakumar E, Nagaraj M, Varalakshmi P
Department of Pharmacology and Toxicology, Tamil Nadu Veterinary and Animal Sciences University, Chennai, 600 007, India.
Comp Biochem Physiol C Toxicol Pharmacol. 2006 Jul;143(3):333-9. doi: 10.1016/j.cbpc.2006.03.008. Epub 2006 Apr 1.
Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. Reactive oxygen species and consequent peroxidative damage caused by aflatoxin are considered to be the main mechanisms leading to hepatotoxicity. The present investigation aims at assessing the hepatoprotective effect of lupeol, a pentacyclic triterpene isolated from the stem bark of Crataeva nurvala, on aflatoxin B(1) (AFB(1))-induced hepatotoxicity in a rat model. The hepatoprotection of lupeol is compared with silymarin, a well known standard hepatoprotectant. Lactate dehydrogenase, alkaline phosphatase, alanine and aspartate aminotransferases were found to be significantly increased in the serum and decreased in the liver of AFB(1) administered (1 mg/kg body mass, orally) rats, suggesting hepatic damage. Marked increase in the lipid peroxide levels and a concomitant decrease in the enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the hepatic tissue were observed in AFB(1) administered rats. Pretreatment with lupeol (100 mg/kg body mass, orally) and silymarin (100 mg/kg body mass, orally) for 7 days reverted the condition to near normalcy. Hepatoprotection by lupeol is further substantiated by the normal histologic findings as against degenerative changes in the AFB(1) administered rats. The results of this study indicate that lupeol is a potent hepatoprotectant as silymarin.
黄曲霉毒素是强效的肝毒性和致癌剂。黄曲霉毒素引起的活性氧及随之而来的过氧化损伤被认为是导致肝毒性的主要机制。本研究旨在评估从瓦氏辣木茎皮中分离出的五环三萜羽扇豆醇对黄曲霉毒素B1（AFB1）诱导的大鼠肝毒性的保肝作用。将羽扇豆醇的保肝作用与著名的标准保肝剂水飞蓟素进行比较。在口服给予AFB1（1毫克/千克体重）的大鼠血清中，乳酸脱氢酶、碱性磷酸酶、丙氨酸氨基转移酶和天冬氨酸氨基转移酶显著升高，而肝脏中这些酶的水平降低，这表明肝脏受到损伤。在给予AFB1的大鼠肝脏组织中，观察到脂质过氧化物水平显著升高，同时酶促抗氧化剂（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶和谷胱甘肽-S-转移酶）和非酶促抗氧化剂（还原型谷胱甘肽、维生素C和维生素E）减少。用羽扇豆醇（100毫克/千克体重，口服）和水飞蓟素（100毫克/千克体重，口服）预处理7天可使情况恢复到接近正常状态。与给予AFB1的大鼠的退行性变化相比，羽扇豆醇的保肝作用通过正常的组织学结果得到进一步证实。本研究结果表明，羽扇豆醇与水飞蓟素一样是一种有效的保肝剂。
