Protective Effect of Diphenyl Diselenide against Methylmercury-Induced Free Radicals in Rat Kidney and Liver Slices
Roos, D. H. 1; Santos, M. 1; Puntel, R. L. 1; Zeni, G. 1; Aschner, M. 2; Rocha, J. B. T. 1;
1Depto. Química- CCNE, Laboratório de Bioquímica Toxicológica, UFSM, SANTA MARIA, RS.
2 Vanderbilt Univ. Sch. Med. Dept. Pediat. B-3307 Med. Ctr. N., Nashville, TN 37232, USA.
The toxicity of methylmercury (MeHg) is associated with the generation of reactive oxygen species (ROS) and reduction in the levels of reduced glutathione (GSH) in a variety of tissues. Organic forms of selenium and tellurium have been suggested as potential antioxidant agents because they exhibit glutathione peroxidase-like activity. The objective of this study was to evaluate the effectiveness of diphenyl diselenide in attenuating MeHg-, buthionine sulfoximine (BSO)- and MeHg+BSO-induced ROS generation in slices derived from rat kidney and liver.
ROS generation was determined spectrofluorometrically, using the fluorescent dye 2’, 7’-dichlorodihydrofluorescin diacetate (DCFA). Renal and hepatic slices (300 mm) were incubated for 2 hours with MeHg and BSO.
MeHg (200 mM) increased (p<0.05) DCFA oxidation in kidney and liver slices (258% and 230%) respectively, as compared to control. BSO (25, 50 and 100 mM), a specific inhibitor of glutamylcysteine synthetase, caused a significant increase (p<0.05) in DCFA oxidation in the liver at all tested concentrations (199%, 181% and 207% respectively). In the kidney, BSO increased (p<0.05) DFCA oxidation only at 100 mM (229%) when compared to control slices. Diphenyl diselenide (5 mM) did not change renal or hepatic DCFA oxidation. However, this organochalcogenide reduced the DCFA oxidation caused by MeHg, BSO or MeHg+BSO to levels indistinguishable from control levels.
The present study corroborates that GSH is an important factor in free radical scavenging, mitigating the BSO-induced increase in ROS generation. Furthermore, the additive effect of MeHg+BSO was greater than the effect of MeHg alone, suggesting reduced intracellular GSH potentiate ROS-mediated injury by MeHg. In this context, diphenyl diselenide at low concentration exhibited antioxidant effect, which may be linked to its antioxidant activity.
Supported by FAPERGS, CNPq, CAPES
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