RESUMO
The action mode of 4,4-diaminodiphenylsulfone (DDS) is still under debate, although it has long been used in treatment of several dermatologic diseases including Hansens disease. In this study, we tested the effect of DDS as an antioxidant on paraquat-induced oxidative stress in non-phagocytic human diploid fibroblasts (HDFs). Overall, preincubation of HDFs with DDS prevented the oxidative stress and the resulting cytotoxic damages caused by paraquat in these cells. The specific effects of DDS in paraquat-treated HDFs are summarized as follows: a) reducing the expression of NADPH oxidase 4 (NOX4) by inhibiting paraquat-induced activation of PKC; b) inhibiting paraquat-induced decreases in mitochondrial complex protein levels as well as in membrane potentials; c) consequently, inhibiting the generation of cytosolic and mitochondrial superoxide anions. Taken together, these findings suggest that DDS would suppress the radical generation in non-phagocytic HDFs during oxidative stress, and that DDS might have the extended potential to be used further in prevention of other oxidative stress-related pathologies.
Assuntos
Dapsona/farmacologia , Diploide , Fibroblastos/citologia , Fibroblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Compostos de Bifenilo/metabolismo , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Sequestradores de Radicais Livres/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , NADPH Oxidase 4 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Paraquat/toxicidade , Fagocitose/efeitos dos fármacos , Picratos/metabolismo , Proteína Quinase C/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxidos/metabolismoRESUMO
Tuberculosis and leprosy are among the most challenging infectious threats to human health. The ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of effective detoxification (pseudoenzymatic) systems. Mycobacterium tuberculosis and Mycobacterium leprae truncated hemoglobins (trHbs) belonging to group I (or N; trHbN) and group II (or O; trHbO) have recently been implicated in the scavenging of nitrogen monoxide (*NO) and peroxynitrite (ONOO-/HOONO). Furthermore, M. leprae trHbO was found to act as an efficient scavenger of the strong oxidant trioxocarbonate(*1-) (CO3*-) following the reaction of peroxynitrite with carbon dioxide (CO2). Here, mechanisms for scavenging of reactive nitrogen species by mycobacterial trHbs are reviewed, and detailed protocols for assessing pseudoenzymatic kinetics are provided.