Probucol as a potent inhibitor of oxygen radical-induced lipid peroxidation and DNA damage:: in vitro studies
Probucol as a potent inhibitor of oxygen radical-induced lipid peroxidation and DNA damage:: in vitro studies
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DOI：
10.1179/135100004225005174
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发表时间：
2004-01-01
期刊：
影响因子：
3.8
通讯作者：
Okada, S
中科院分区：
文献类型：
--
作者：
Iqbal, M;Sharma, SD;Okada, S
普罗布考是一种临床常用的降胆固醇和抗氧化药物，研究其对氮基三乙酸铁（Fe-NTA）和过氧化氢（H2 O2）诱导的脂质过氧化和DNA损伤的保护作用。Fe-NTA是一种有效的肾毒性剂，通过催化H2 O2衍生的羟基自由基的分解产生，诱导急性和亚急性肾近端小管坏死，已知羟基自由基会导致脂质过氧化和DNA损伤。Fe-NTA与啮齿类动物肾腺癌的高发病率相关。脂质过氧化和DNA损伤是Fe-NTA毒性的主要表现，普罗布考可减轻其毒性。在Fe-NTA（0.1 mM）存在下，将肾微粒体膜和/或小牛胸腺DNA与H2 O2（40 mM）孵育，可诱导肾微粒体脂质过氧化和DNA损伤，分别为对照组的2.4倍和5.9倍（P < 0.05）。普罗布考以浓度依赖性方式抑制肾微粒体脂质过氧化和DNA损伤的诱导。在脂质过氧化保护研究中，普罗布考处理显示出浓度依赖性抑制（10-34%抑制; P
Probucol, a clinically used cholesterol lowering and antioxidant drug, was investigated for possible protection against lipid peroxidation and DNA damage induced by iron nitrilotriacetate (Fe-NTA) plus hydrogen peroxide (H2O2). Fe-NTA is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of H2O2-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. Fe-NTA is associated with a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation and DNA damage are the principal manifestation of Fe-NTA induced toxicity, which could be mitigated by probucol. Incubation of renal microsomal membrane and/or calf thymus DNA with H2O2 (40 mM) in the presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA damage to about 2.4-fold and 5.9-fold, respectively, as compared to control (P < 0.05). Induction of renal microsomal lipid peroxidation and DNA damage was inhibited by probucol in a concentration-dependent manner. In lipid peroxidation protection studies, probucol treatment showed a concentration-dependent inhibition (10-34% inhibition; P