p-Methoxyl-diphenyl diselenide protects against cisplatin-induced renal toxicity in mice |
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Authors: | Ethel A. Wilhelm Cristiani F. BortolattoCristina W. Nogueira |
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Affiliation: | Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil |
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Abstract: | The present study was designed to investigate the effects of p-methoxyl-diphenyl diselenide (OMePhSe)2 on oxidative stress and renal damage parameters of mice exposed to cisplatin. (OMePhSe)2 (50 and 100 mg/kg/day) was orally administered to mice for six consecutive days. On the third day after the beginning of (OMePhSe)2 treatment, the renal toxicity was induced by injecting cisplatin (10 mg/kg intraperitoneal) in mice. (OMePhSe)2 treatment (50 mg/kg) partially reduced plasma urea and creatinine levels increased by cisplatin. Histopathological examination of kidneys showed that (OMePhSe)2 ameliorated renal injury caused by cisplatin. (OMePhSe)2 attenuated the decrease in reduced glutathione (GSH) and ascorbic acid (AA) levels, the inhibition of glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and catalase (CAT) activities caused by cisplatin in kidney. (OMePhSe)2 treatment partially protected against the inhibition of renal δ-aminolevulinic dehydratase (δ-ALA-D) activity caused by cisplatin. No alteration in renal lipid peroxidation levels was found in cisplatin and/or (OMePhSe)2 groups. (OMePhSe)2 was effective against the increase in reactive species (RS) levels caused by the cisplatin exposure. Based on the renoprotective and antioxidant actions of (OMePhSe)2 we suggest that this organoselenium compound could be considered a feasible candidate to protect against toxicity commonly encountered in cisplatin exposure. |
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Keywords: | (OMePhSe)2, p-methoxyl-diphenyl diselenide GSH, reduced glutathione AA, ascorbic acid GPx, glutathione peroxidase GST, glutathione S-transferase GR, glutathione reductase CAT, catalase δ-ALA-D, δ-aminolevulinic dehydratase SH, sulfhydryl SDS, sodium dodecyl sulfate TBARS, thiobarbituric acid reactive species MDA, malondialdehyde TCA, trichloroacetic acid OPA, o-phthalaldehyde GSSG, oxidized glutathione CDNB, 1-chloro-2,4-dinitrobenzene ROS, reactive oxygen species NMR, nuclear magnetic resonance GC/MS, gas chromatography/mass spectrometry DCHF-DA, 2&prime ,7&prime -dichlorofluorescein diacetate DCF, dichlorofluorescein |
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