title: Protective effects of organoselenium compounds against methylmercury-induced oxidative stress in mouse brain mitochondrial-enriched fractions.
abstract: We evaluated the potential neuroprotective effect of 1-100 µM of four organoselenium compounds: diphenyl diselenide, 3'3-ditri-fluoromethyldiphenyl diselenide, p-methoxy-diphenyl diselenide, and p-chloro-diphenyl diselenide, against methylmercury-induced mitochondrial dysfunction and oxidative stress in mitochondrial-enriched fractions from adult Swiss mouse brain. Methylmercury (10-100 µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, which occurred in parallel with increased glutathione oxidation, hydroperoxide formation (xylenol orange assay) and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with diphenyl diselenide (100 µM) completely prevented the disruption of mitochondrial activity as well as the increase in TBARS levels caused by methylmercury. The compound 3'3-ditrifluoromethyldiphenyl diselenide provided a partial but significant protection against methylmercury-induced mitochondrial dysfunction (45.4 ± 5.8% inhibition of the methylmercury effect). Diphenyl diselenide showed a higher thiol peroxidase activity compared to the other three compounds. Catalase blocked methylmercury-induced TBARS, pointing to hydrogen peroxide as a vector during methylmercury toxicity in this model. This result also suggests that thiol peroxidase activity of organoselenium compounds accounts for their protective actions against methylmercury-induced oxidative stress. Our results show that diphenyl diselenide and potentially other organoselenium compounds may represent important molecules in the search for an improved therapy against the deleterious effects of methylmercury as well as other mercury compounds.
authors: Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors: D F
authors: DF
authors: Meinerz
authors: M T
authors: MT
authors: de Paula
authors: B
authors: B
authors: Comparsi
authors: M U
authors: MU
authors: Silva
authors: A E
authors: AE
authors: Schmitz
authors: H C
authors: HC
authors: Braga
authors: P S
authors: PS
authors: Taube
authors: A L
authors: AL
authors: Braga
authors: J B T
authors: JB
authors: Rocha
authors: A L
authors: AL
authors: Dafre
authors: M
authors: M
authors: Farina
authors: J L
authors: JL
authors: Franco
authors: T
authors: T
authors: Posser
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002458:Cell Fractionation; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D020262:Mercury Poisoning, Nervous System / Q000517:prevention & control*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000145:classification / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D001555:Benzene Derivatives; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C061132:diphenyldiselenide