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Protective Effect of Organochalcogens Against Ca2+-Induced Free Radicals Generation in Isolated Mitochondria From Different Rat Tissues
Puntel, R. L.; Roos, D. H.; Zeni, G.; Nogueira, C. W.; Rocha, J. B. T.
Depto. Química- CCNE, Laboratório de Bioquímica Toxicológica, UFSM, SANTA MARIA, RS.
Calcium (Ca2+) homeostasis is an essential mechanism to physiological processes. During Ca2+ signaling, transient increases in cytosolic calcium may occur and induce mechanisms of Ca2+ buffering. Mitochondrial Ca2+ uptake is one of the mechanisms activated to buffer cytosolic Ca2+. An increase and accumulation of mitochondrial Ca2+ trigger the aperture of a permeability transition pore (PTP) through of reactive oxygen species (ROS) generated during the Ca2+ buffering by mitochondria. Organic forms of selenium and tellurium have been suggested as possible antioxidant agents because they exhibit glutathione peroxidase-like activity and oxidize thiols during the reduction of H2O2. The aim of this study was to investigate whether diphenyl diselenide and diphenyl ditelluride could protect mitochondria isolated from rat brain, liver and kidney from Ca2+-induced free radical generation.
Mitochondrial release of ROS (H2O2) was determined spectrofluorometrically, using the membrane-permeable fluorescent dye 2', 7'-dichlorodihydrofluorescin diacetate (DCFA). Fluorescence was determined at 488 nm for excitation and 520 nm for emission. Data were analyzed statistically by one-way ANOVA, followed by Duncan's Multiple Range Test when appropriate.
Ca2+ (160mM) caused a significant increase in DCFA oxidation as compared to control (p<0.05), either in brain or in liver and kidney. Dimethyl sulfoxide (DMSO, vehicle) did not cause any effect per se in tissues studied as compared to Ca2+ (p>0.05). Diphenyl diselenide caused a significant reduction in Ca2+-induced DCFA oxidation in rat brain and kidney mitochondria when compared to DMSO (p<0.05) at 5mM onwards (5-100 mM). Likewise, diphenyl diselenide caused a significant reduction in Ca2+-induced DCFA oxidation in rat liver mitochondria at 10mM onwards. In a similar way, diphenyl ditelluride caused a significant reduction in Ca2+-induced DCFA oxidation in rat brain, liver and kidney preparations when compared to DMSO (p<0.05) at all tested concentrations (5- 100mM).
Taken together, the presented results support the potential protective properties of organochalcogens against Ca2+-induced DCFA oxidation.
Supported by FAPERGS, CNPq, CAPES
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