Altered pH homeostasis modulates the glutathione peroxidase mimics and other antioxidant properties of diphenyl diselenide.

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.