Faculty of Education, Kumamoto University, 2-40-1 Kurokami, Kumamoto 860-8555, Japan.
Toxicol In Vitro. 2012 Mar;26(2):252-7. doi: 10.1016/j.tiv.2011.12.007. Epub 2011 Dec 14.
The purpose of this study is to elucidate the possible mechanism of superoxide formation through redox cycling of plumbagin (PLG) in pig heart. Of four 1,4-naphthoquinones tested in this study, PLG was most efficiently reduced in the cytosolic fraction of pig heart. On the other hand, lawsone (LAS) was little reduced. Thus, whether or not PLG and LAS induce the formation of superoxide anion radical in pig heart cytosol was examined, by using the methods of cytochrome c reduction and chemiluminescence. PLG significantly induced the formation of superoxide anion radical, even though LAS had no ability to mediate superoxide formation. PLG was a significant inhibitor for the stereoselective reduction of 4-benzoylpyridine (4-BP) catalyzed by tetrameric carbonyl reductase (TCBR) in pig heart cytosol. Furthermore, PLG was confirmed to competitively inhibit the 4-BP reduction, and the optimal pH for the PLG reduction was around 6.0 similar to that for the 4-BP reduction. These results suggest that PLG mediates superoxide formation through its redox cycling involved in the two-electron reduction catalyzed by TCBR, and induces oxidative stress in pig heart.
本研究旨在阐明通过还原吡咯并萘醌（PLG）在猪心的氧化还原循环形成超氧阴离子自由基的可能机制。在本研究中测试的四种 1,4-萘醌中，PLG 在猪心胞质部分被最有效地还原。另一方面，莱苏尔（LAS）几乎没有被还原。因此，通过使用细胞色素 c 还原和化学发光的方法，检查了 PLG 和 LAS 是否在猪心胞质中诱导超氧阴离子自由基的形成。PLG 显著诱导超氧阴离子自由基的形成，尽管 LAS 没有介导超氧形成的能力。PLG 是猪心胞质中四聚羰基还原酶（TCBR）催化的 4-苯甲酰吡啶（4-BP）立体选择性还原的有效抑制剂。此外，PLG 被证实竞争性抑制 4-BP 还原，PLG 还原的最佳 pH 值约为 6.0，与 4-BP 还原的最佳 pH 值相似。这些结果表明，PLG 通过其涉及 TCBR 催化的两电子还原的氧化还原循环介导超氧形成，并在猪心诱导氧化应激。
