L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats

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.