Brazilian Journal of Pharmaceutical Sciences
versión impresa ISSN 1984-8250
MORAES, Natália Valadares de et al. L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats. Braz. J. Pharm. Sci. [online]. 2012, vol.48, n.1, pp. 87-94. ISSN 1984-8250. http://dx.doi.org/10.1590/S1984-82502012000100010.
Dapsone use is frequently associated to hematological side effects such as methemoglobinemia and hemolytic anemia, which are related to N-hydroxylation mediated by the P450 enzyme system. The aim of the present study was to evaluate the influence of L-arginine supplementation, a precursor for the synthesis of nitric oxide, as single or multiple dose regimens on dapsone-induced methemoglobinemia. Male Wistar rats were treated with L-arginine at 5, 15, 30, 60 and 180 mg/kg doses (p.o., gavage) in single or multiple dose regimens 2 hours prior to dapsone administration (40 mg/kg, i.p.). The effect of the nitric oxide synthase inhibitor L-NAME was investigated by treatment with multiple doses of 30 mg/kg (p.o., gavage) 2 hours before dapsone administration. Blood samples were collected 2 hours after dapsone administration. Erythrocytic methemoglobin levels were assayed by spectrophotometry. The results showed that multiple dose supplementations with 5 and 15 mg/kg L-arginine reduced dapsone-induced methemoglobin levels. This effect is mediated by nitric oxide formation, since the reduction in methemoglobin levels by L-arginine is blocked by simultaneous administration with L-NAME, a nitric oxide synthase inhibitor.
Palabras llave : Dapsone; Methemoglobinemia; L-arginine; Nitric oxide; L-NAME.