Ogunmoyole T, Rocha J B T, Okoronkwo A E, Kade I J
Department of Biochemistry, Federal University of Technology, FUTA Road, off Ilesha Road, PMB 704 Akure, Ondo State, Nigeria.
Chem Biol Interact. 2009 Dec 10;182(2-3):106-11. doi: 10.1016/j.cbi.2009.08.018. Epub 2009 Sep 6.
Recent evidences have shown that the in vivo antioxidant chemistry of organoselenium compounds such as diphenyl diselenide (DPDS) is complex and it is not completely understood. The complexity is partly due to the fact that DPDS is generally thought to exert its antioxidant action by mimicking glutathione peroxidase (GPx) with concomitant utilization of glutathione (GSH) in vitro. In contrast to in vitro data, we recently observed that DPDS increases rather than diminish GSH levels in diabetic models. The present study therefore sought to investigate a possible change in the antioxidant mechanisms of DPDS in changing physiological pH that may be associated with hyperglycaemia. The results show that in all the pHs tested (acidic, neutral or basic), DPDS did not exhibit either free radical scavenging ability or Fe2+ chelating effect. However, DPDS exhibited increasing ability to reduce Fe3+ with increasing pH. On the other hand, the GPx mimic of DPDS was maximal at physiological pH and totally abolished in the acidic medium. Furthermore, we observed that irrespective of the pH of the medium, DPDS significantly inhibited both deoxyribose degradation under H2O2 and Fe2+ assault and lipid peroxidation induced by either Fe2+ or sodium nitroprusside; suggesting that the antioxidant mechanism of DPDS in the acidic medium may not be related to its generally accepted GPx mimic. Taken together, we speculate that the antioxidant mechanism of DPDS against macromolecular damage in biological system is complex and may not be strictly related to its GPx mimic, a mechanism generally regarded as the most important antioxidant mechanism of organoselenium compounds.
最近的证据表明，二苯基二硒醚（DPDS）等有机硒化合物的体内抗氧化化学过程很复杂，尚未完全明确。这种复杂性部分源于以下事实：一般认为DPDS在体外通过模拟谷胱甘肽过氧化物酶（GPx）并伴随利用谷胱甘肽（GSH）来发挥其抗氧化作用。与体外数据相反，我们最近观察到在糖尿病模型中DPDS会升高而非降低GSH水平。因此，本研究旨在探究在可能与高血糖相关的生理pH值变化时DPDS抗氧化机制的潜在变化。结果表明，在所有测试的pH值（酸性、中性或碱性）下，DPDS既未表现出自由基清除能力，也未表现出Fe2+螯合作用。然而，随着pH值升高，DPDS还原Fe3+的能力增强。另一方面，DPDS模拟GPx的能力在生理pH值时最大，在酸性介质中则完全消失。此外，我们观察到，无论介质的pH值如何，DPDS均能显著抑制H2O2和Fe2+攻击下的脱氧核糖降解以及Fe2+或硝普钠诱导的脂质过氧化；这表明DPDS在酸性介质中的抗氧化机制可能与其普遍认可的模拟GPx无关。综上所述，我们推测DPDS在生物系统中对抗大分子损伤的抗氧化机制很复杂，可能与其模拟GPx的作用并无严格关联，而模拟GPx通常被认为是有机硒化合物最重要的抗氧化机制。
