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Efeito protetor de antioxidantes na metemoglobina e no dano em dna induzidos pela dapsona-hidroxilamina in vitro
(Universidade Federal do Pará, 2016-06-21) GOMES, Antonio Rafael Quadros; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390
Dapsone (DDS) is one of the drugs used in polychemotherapy of leprosy associated with rifampicin and clofazimine. Of these drugs, DDS is primarily responsible for adverse reactions, such as methemoglobinemia and hemolytic anemia. These reactions are related to the DDS metabolite, dapsone hydroxylamine (DDS-NOH). In an attempt to promote the reduction of toxic effects are studied alternative therapies with antioxidants. This work aimed to evaluate the protective effect of N-acetylcysteine (NAC), A. brasiliensis and Glutathione ethyl ester (GSH-EE) in methemoglobin (MetHb) and DNA damage induced by DDS-NOH in vitro , correlating to oxidative stress parameters. For this, suspensions of human erythrocytes to 50% were pre- and post-treated with NAC, A. brasiliensis and GSH-EE in different concentrations, being exposed groups DDS-NOH to induce the formation MetHb. It also assessed whether the activity of enzymes-SOD and CAT and GSH levels, TEAC and MDA. In leukocytes evaluated the induction of ROS intracellularly using DCFH-DA and the damage to DNA by comet assay. The results showed that the DDS-NOH metabolite was capable of inducing MetHb in vitro, this dose-dependent effect. Regarding the pre-treatment, all the antioxidants prevented MetHb formation induced by DDS-NOH, as well as post-treatment. For SOD, only the pre-treatment with NAC and A. brasiliensis reduced SOD activity. In the post-treatment, there was increased when treated with antioxidants. Pre-treatment with NAC and GSH-EE increased CAT activity, moreover A. brasiliensis reduced, as after treatment with antioxidants. As for GSH levels, pre-treatment with NAC and GSH increased A. brasiliensis, on the other hand, did not alter after treatment. Regarding TEAC did not change. With respect to oxidative damage in the pre-treatment A. brasiliensis and GSH-EE reduced MDA. In the post-treatment, there was an increase in group A. brasiliensis and reduced GSH-EE group. Only the NAC was shown to be effective in removing the intracellular ROS induced by DDS-NOH in leukocytes. While in erythrocytes, a NAC and A. brasiliensis were able to reduce this effect. In the study of the comet assay, the DDS-NOH was able to induce DNA damage in peripheral blood leukocytes, however this damage was reduced when treated with NAC and A. brasiliensis. It can be concluded from our data that the evaluated antioxidants have therapeutic potential in the prevention of MetHb and DNA damage induced by DDS-NOH in vitro, more effective NAC against these effects.