In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage
In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage
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DOI：
10.1002/tcm.10070
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Okada, S
中科院分区：
文献类型：
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作者：
Iqbal, M;Okazaki, Y;Okada, S
许多研究表明，自由基参与了各种致病过程，包括致癌的起始/促进阶段，因此抗氧化剂被认为是一种保护剂。铁螯合物，氮基三乙酸铁（Fe-NTA），是一种强效的肾毒性药物，通过催化过氧化氢衍生的羟基自由基的分解，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。后者与啮齿类动物肾腺癌的高发病率有关。脂质过氧化和DNA损伤是Fe-NTA毒性的主要表现，抗氧化剂可减轻其毒性。因此，在这项研究中，我们研究了姜黄素，一种多酚化合物从姜黄可能对脂质过氧化和DNA损伤的保护Fe-NTA和过氧化氢在体外诱导的效果。在Fe-NTA（0.1 mM）存在下，肾微粒体膜和/或小牛胸腺DNA与过氧化氢（40 mM）孵育诱导肾微粒体脂质过氧化和DNA损伤，与生理盐水处理的对照组相比，分别约为2.2倍和5.6倍（P
A number of investigations have implicated the involvement of free radicals in various pathogenic process including initiation/promotion stages of carcinogenesis and antioxidants have been considered to be a protective agent for this reason. An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of hydrogen peroxide-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. The latter 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 antioxidants. In this study, we therefore investigated the effect of curcumin, a polyphenolic compound from Curcuma longa for a possible protection against lipid peroxidation and DNA damage induced by Fe-NTA and hydrogen peroxide in vitro. Incubation of renal microsomal membrane/and or calf thymus DNA with hydrogen peroxide (40 mM) in the presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA damage to about 2.2-and 5.6-fold, respectively, as compared to saline treated control (P