THE PROTECTIVE EFFECTS OF EUGENOL ON CARBON-TETRACHLORIDE INDUCED HEPATOTOXICITY IN RATS
THE PROTECTIVE EFFECTS OF EUGENOL ON CARBON-TETRACHLORIDE INDUCED HEPATOTOXICITY IN RATS
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DOI：
10.3109/10715769509065281
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发表时间：
1995-01-01
影响因子：
3.3
通讯作者：
LAKSHMAIAH, N
中科院分区：
文献类型：
--
作者：
NAGABABU, E;SESIKERAN, B;LAKSHMAIAH, N
我们早期的体外研究表明，丁子香酚可抑制肝微粒体单加氧酶活性和四氯化碳 (CCl4) 诱导的脂质过氧化（Free Rad. Res. 20, 253-266, 1994）。本研究的目的是研究丁子香酚对 CCl4 毒性的体内保护作用。连续 3 天口服丁子香酚（5 或 25 mg/kg 体重）不会改变血清谷氨酸草乙酸转氨酶 (SGOT)、微粒体酶如细胞色素 P-450 还原酶、葡萄糖 6 磷酸酶 (G-6-Pase) 异生素代谢酶（氨基比林）的水平 N-脱甲基酶、N-亚硝基二甲胺脱甲基酶和乙氧基试卤灵-O-脱乙基酶）和肝脏组织学。在连续三天，即48小时、24小时和30分钟，在单次口服CCl4（2.5ml/kg体重）之前，向每只大鼠胃内给予一定剂量的丁子香酚（5或25mg/kg），可防止SGOT水平升高，而肝脏形态变化没有明显改善。丁子香酚预处理也不影响CCl4引起的微粒体细胞色素P-450含量、G-6-Pase和外源代谢酶的降低。由于丁子香酚在体内迅速代谢和清除，因此在另一项实验中修改了剂量方案，口服三次丁子香酚（0.2、1.0、5.0或25 mg/kg），即腹膜内注射之前（-1小时）、（0小时）和之后（+3小时）。 CCl4 (0.4 ml/kg) 的施用显着阻止了 SGOT 活性的升高以及肝坏死。 1 mg 和 5 mg 丁子香酚剂量的保护作用更为明显。然而，丁子香酚并不能阻止 CCl4 处理引起的微粒体 G-6-Pase 活性的降低，这表明对内质网的损伤没有得到保护。丁子香酚对 CCl4 诱导的肝毒性的保护作用在 CCl4 治疗的同时或之后不久而不是在 CCl4 治疗之前不久给予时更为明显。
Our earlier studies in vitro have shown that eugenol inhibits liver microsomal monooxygenase activities and carbon tetrachloride (CCl4)-induced lipid peroxidation (Free Rad. Res. 20, 253-266, 1994). The objective of the present investigation was to study the in vivo protective effect of eugenol against CCl4 toxicity. Eugenol (5 or 25 mg/kg body wt) given orally for 3 consecutive days did not alter the levels of serum glutamic oxalacetic transaminase (SGOT), microsomal enzymes such as cytochrome P-450 reductase, glucose-6-phosphatase (G-6-Pase) xenobiotic-metabolizing enzymes (aminopyrine N-demethylase, N-nitrosodimethylamine-demethylase and ethoxyresorufin-O-deethylase) and liver histology. Doses of eugenol (5 or 25 mg/kg) administered intragastrically to each rat on three consecutive days i.e. 48 hr, 24 hr and 30 min before a single oral dose of CCl4 (2.5 ml/kg body wt) prevented the rise in SGOT level without appreciable improvement in morphological changes in liver. Eugenol pretreatment also did not influence the decrease in microsomal cytochrome P-450 content, G-6-Pase and xenobiotic-metabolizing enzymes brought about by CCl4. Since eugenol is metabolized and cleared rapidly from the body, the dose schedule was modified in another experiment, Eugenol (0.2, 1.0, 5.0 or 25 mg/kg) when given thrice orally i.e. prior to (-1 hr) along with (0 hr) and after (+3 hr) the i.p. administration of CCl4 (0.4 ml/kg) prevented significantly the rise in SGOT activity as well as liver necrosis. The protective effect was more evident at 1 mg and 5 mg eugenol doses. However, the decrease in microsomal G-6-Pase activity by CCl4 treatment was not prevented by eugenol suggesting that the damage to endoplasmic reticulum is not protected. The protective effect of eugenol against CCl4 induced hepatotoxicity is more evident when it is given concurrently or soon after rather than much before CCl4 treatment.