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.

Bibliographic Details

Main Authors:	Moraes,Natália Valadares de, Bergamaschi,Mateus Machado, Bianchi,Maria de Lourdes Pires, Bragheto,Juliana Bordinassi, Malfará,Wilson Roberto, Queiroz,Regina Helena Costa
Format:	Digital revista
Language:	English
Published:	Universidade de São Paulo, Faculdade de Ciências Farmacêuticas 2012
Online Access:	http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502012000100010
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