Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae

Abstract

Humans are usually exposed to organic form of mercury, the organometallic cation methylmercury ([CH3Hg]+, MeHg), by eating fish and seafood. The neurotoxic effects of MeHg are already widely known. Individuals exposed to high concentrations of this compound showed sensory disorders in the hands and feet, hearing and visual impairment, weakness and, in extreme cases, paralysis and death. Although the exact mechanisms underlying the toxicity of MeHg are not yet completely understood, there is evidence that oxidative stress plays a central role. The organic compound derived from selenium, diphenyl diselenide [(PhSe)2] is a simple electrophilic synthetic intermediate in the synthesis of various organic compounds of pharmaceutical interest containing selenium and have already presented antioxidant, anti-nociceptive, anti-inflammatory, antihyperglycemic, antiteratogenic, among others properties. The aim of this study was to investigate some mechanisms involved in the protective effect of (PhSe)2 on the toxicity induced by MeHg, using wild and knockout strains of S. cerevisiae for different enzymes and proteins linked to the antioxidant defense system. Using these strains, as well as different concentrations (PhSe)2 and/or MeHg, the specific objectives of this study were: i) to evaluate the growth inhibition; ii) to quantify the production of reactive oxygen species; iii) to evaluate the permeability of cell membranes; iv) to quantify the intracellular GSH content. This study sheds light on the mechanisms involved in the protection of diphenyl diselenide against MeHg indicating the involvement of the antioxidant defense system of S. cerevisiae and the sequestering of Hg in (PhSe)2 protection. The compound diphenyl diselenide protects against the toxicity induced by methylmercury, as noted in the recovery of growth and lower levels of reactive oxygen species, membrane permeability and restoration of intracellular GSH content in yeasts treated with both compounds. The protective effect triggered by diphenyl diselenide seems to be related with the activation of some enzymes of antioxidant system of yeasts. Not all analyzed antioxidant enzymes had the same participation or importance in the protection mechanism. Functional and genetic similarities between yeast and mammalian cells suggests that the elucidation of these mechanisms will help direct the search to human.