RESUMO
Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.
Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Retinose Pigmentar/tratamento farmacológico , Acetilcisteína/administração & dosagem , Administração Oral , Administração Tópica , Animais , Antioxidantes/administração & dosagem , Catalase/metabolismo , Sobrevivência Celular , Modelos Animais de Doenças , Eletrorretinografia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estresse Oxidativo/efeitos dos fármacos , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/patologia , Retinose Pigmentar/patologia , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Fatores de Tempo , Regulação para CimaRESUMO
Formetanate hydrochloride is a bifunctional pesticide with remarkable solubility, high toxicity, and potential mobility in aqueous environments. The relative stability of the formamidine and carbamate groups in this compound can be used to predict the identity of its degradation products in water. The reported NMR and UV-vis spectroscopic studies revealed that the formamidine group is more labile than the carbamate group under strongly basic conditions, as well as under predetermined field conditions. The half-life of the formamidine group was determined to be 3.9 h under strongly basic conditions (pH 12.6) and 14.4 h under mildly basic conditions (pH 7.6). The longevity of the carbamate group may exceed 6 months due its resistance to base-promoted degradation. These results may be used in the design of more specific remediation technology for formetanate-contaminated surface water.
