Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver
Inhibitory effect of esculetin on oxidative damage induced by t-butyl hydroperoxide in rat liver
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DOI：
10.1007/s002040000148
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发表时间：
2000-10-01
影响因子：
6.1
通讯作者：
Tseng, TH
中科院分区：
文献类型：
--
作者：
Lin, WL;Wang, CJ;Tseng, TH
越来越多关于自由基生成剂和炎症过程的证据表明，活性氧的积累可能导致肝毒性。脂质氢过氧化物的短链类似物叔丁基氢过氧化物 (t-BHP) 可被肝细胞中的细胞色素 P-450 代谢为自由基中间体，进而引发脂质过氧化，影响细胞完整性并导致细胞损伤。在本研究中，我们使用 t-BHP Co 在体外和体内诱导肝毒性，并测定了七叶亭（一种香豆素化合物）的抗氧化生物活性。我们的研究表明，用七叶亭（5-20 μg/ml）预处理可显着减少乳酸脱氢酶（LDH）和丙氨酸转氨酶（ALT）的泄漏，并减少用t-BHP处理30分钟诱导的原代培养大鼠肝细胞中丙二醛（MDA）的形成。一项大鼠体内研究表明，在单次腹膜内注射之前，用浓度为 0.5 和 5 mg/kg 的七叶亭（腹腔注射）预处理 5 天， t-BHP 剂量（0.1 mmol/kg）显着降低了肝酶标志物（ALT 和 AST）的血清水平，并减少了肝脏的氧化应激。对大鼠肝脏的组织病理学评估表明，七叶亭可降低 t-BHP 引起的肝脏病变的发生率，包括肝细胞肿胀、白细胞浸润和坏死。基于上述结果，我们推测七叶亭可能通过减少生命系统中的氧化应激发挥化学预防作用。
Increasing evidence regarding free radical-generating agents and inflammatory processes suggests that accumulation of reactive oxygen species can cause hepatotoxicity. A short-chain analog of lipid hydroperoxide, t-butyl hydroperoxide (t-BHP), can be metabolized to free radical intermediates by cytochrome P-450 in hepatocytes, which in turn can initiate lipid peroxidation, affect cell integrity and result in cell injury. In this study, we used t-BHP Co induce hepatotoxicity in vitro and in vivo and determined the antioxidative bioactivity of esculetin, a coumarin compound. Our investigations showed that pretreatment with esculetin (5-20 mug/ml) significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine transaminase (ALT), and also decreased the formation of malondialdehyde (MDA) in primary cultured rat hepatocytes induced by a 30-min treatment with t-BHP. An in vivo study in rats showed that pretreatment with esculetin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of the hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that esculetin reduced the incidence of liver lesions induced by t-BHP, including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that esculetin may play a chemopreventive role via reducing oxidative stress in living systems.