Effects of H2-receptor antagonists on dapsone-induced methaemoglobinaemia in rats

Malfará, Wilson Roberto; Pereira, Carolina Paula; Santos, Antônio Cardozo dos; Queiróz, Regina Helena Costa

doi:10.1006/phrs.2002.0958

Cited by 8 publications

(6 citation statements)

References 22 publications

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“…Several alternative modalities for the treatment of methemoglobinemia, including N-acetylcysteine, ascorbic acid, sodium thiosulfate, and cytochrome P-450 inhibitor, have been suggested (6,(26)(27)(28)(29)(30); however, the studies that evaluated these treatments were all preliminary and the reported results were inconclusive or ineffective. In this study, we demonstrated that a single dose of EP was effective at reducing the concentration of metHgb.…”

Section: Discussionmentioning

confidence: 94%

“…Dapsone is primarily metabolized by both N-acetylation and N-hydroxylation. The hematologic side effects of dapsone have been shown to be a consequence of N-hydroxylation via the 3A family of isoenzymes or CYP2E1 of the hepatic cytochrome P-450 system, which leads to the production of hydroxylamine (4)(5)(6)(7). Hydroxylamine then reacts with O 2 to form oxygen-free radicals and methemoglobin (8,9).…”

Section: Introductionmentioning

confidence: 98%

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The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats

Kwon

Lee³

et al. 2008

Clinical Toxicology

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 98%

The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats

Kwon

Lee³

et al. 2008

Clinical Toxicology

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“…Ascorbic acid, better known as vitamin C, is one alternative due to its antioxidant effects. 22 Other investigatory therapies include N-acetylcysteine 23 and cytochrome P-450 inhibitors in dapsoneinduced methemoglobinemia, 24 although studies remain limited. Treating the underlying cause behind the production of methemoglobin, such as the oxidative stress in G6PD deficiency, can also be a form of treatment.…”

Section: Discussionmentioning

confidence: 99%

Sometimes, It’s Just Black and White: Dark Urine and Pallor in a 2-Year-Old Boy

Wadowski

Chang

Khan

et al. 2016

Hospital Pediatrics

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A 2-year-old Chinese boy was admitted to the hospital after 2 days of pallor and fatigue and 1 day of dark urine. There was no recent history of illness, although his mother reported a 1-week history of intermittent, subjective fevers. There was no history of recent travel, no history of recent trauma, no sick contacts, no pertinent family history, no changes in diet, and no medications. His past medical history was significant for self-limited nosebleeds, which had increased in frequency over the few days before admission. On examination, the patient was afebrile and tachycardic, with an oxygen saturation of 88% on room air. He was pale and tired-appearing on arrival. He was in no respiratory distress, and there was no hepatosplenomegaly or lymphadenopathy. His skin examination was notable for jaundice, but there were no bruises, petechiae, or rash. He was noted to pass cola-colored urine while in the hospital. His chest radiograph was normal. Laboratory evaluation revealed a normal serum electrolyte level and normal serum urea nitrogen and creatinine levels. A complete blood count (CBC) revealed the following: a white blood cell count of 20,700 per mL with normal differential, hemoglobin of 4.1 g/dL, hematocrit of 11.8%, a platelet count of 365 000 per mL, a mean corpuscular volume of 88.2 femtoliters, and a red cell distribution width of 20.5%. Question What Are the Current Recommendations for the Evaluation of Anemia in the Pediatric Population? Discussion Anemia is estimated to affect up to 20% of the American population during childhood. 1 It can be defined on the basis of age-and sex-specific percentile criteria for hemoglobin concentration. The Centers for Disease Control and Prevention, for example, uses the fifth percentile and below to define anemia, resulting in a lower limit of normal range of 11.0 to 11.9 g/dL for children under age 12 and 12.5 to 13.5 g/dL for children ages 12 to 18 years. 2 Reference ranges for neonates vary considerably on the basis of factors such as gestational age and day of life, although standardized reference values have been established. 3 The diagnostic approach to anemia combines a thorough history and physical examination with laboratory testing aimed at identifying which cell lines are affected, characterizing the patient' s erythrocytes, and differentiating between aplastic and consumptive processes. The CBC, which is used to confirm the presence of anemia, will also reveal whether the patient has abnormalities in the leukocyte or thrombocyte lines. Several acquired or inherited diseases can contribute to peripheral cytopenia, and many,

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“…et al., 1998), cimetidine Malfará et al, 2002), riboflavin (Dötsch et al, 2000), α-lipoic acid (Coleman, Taylor, 2003), sodium thiosulfate (Matteucci et al, 2003), ethyl pyruvate (Jo et al, 2008) and N-acetylcysteine (Wright et al, 1996;Wright et al, 1998;Dötsch et al, 2000;Tanen et al, 2000;De Moraes et al, 2008). N-acetylcysteine, a precursor of glutathione, used in combination with DDS in rats, has shown increased methemoglobin levels in these animals compared to rats treated with DDS alone.…”

Section: Discussionmentioning

confidence: 99%

“…The various attempts to reduce methemoglobinemia have included: preventing CYP-mediated oxidative metabolism of xenobiotics to hydroxylamines Malfará et al, 2002); biochemical attenuation of metHb formation with antioxidants (Prussick et al, 1992; Wright et al, 1996;Dötsch et al, 1998;Wright et al, 1998;Dötsch et al, 2000;Tanen et al, 2000; Matteuci et al, 2003;De Moraes et al, 2008;Jo et al, 2008); and reduction of metHb to hemoglobin by stimulating NADH diaphorase or NADPH diaphorase (Dötsch et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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

Moraes

Bergamaschi

Bianchi

et al. 2012

Braz. J. Pharm. Sci.

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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 dapsoneinduced 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. Uniterms:Dapsone. Methemoglobinemia. L-arginine. Nitric oxide. L-NAME.O uso da dapsona é frequentemente associado a efeitos adversos hematológicos, como a metemoglobinemia e anemia hemolítica, ambos relacionados com a N-hidroxilação mediada pelo sistema P450. O objetivo do estudo foi avaliar a influência da suplementação de L-arginina, um precursor da síntese de óxido nítrico, administrado em regime de dose única ou múltipla na metemoglobinemia induzida pela dapsona. Ratos machos Wistar foram tratados com L-arginina (po, gavagem) em dose única ou múltipla de 5, 15, 30, 60 e 180 mg/kg 2 horas antes da administração de dapsona (40 mg/kg, ip). O efeito do L-NAME, um inibidor de óxido nítrico sintase (NOS), foi avaliado através do tratamento com doses múltiplas de 30 mg/kg. Amostras de sangue foram coletadas duas horas após a administração de dapsona. A concentração de metemoglobina eritrocitária foi analisada por espectrofotometria. Os resultados mostraram que a suplementação em dose múltipla de 5 e 15 mg/kg de L-arginina reduziu os níveis de metemoglobina induzida pela dapsona. Este efeito é mediado pela formação de óxido nítrico, uma vez que a redução nos níveis de metemoglobina pela L-arginina é bloqueada pela administração simultânea de L-NAME, um inibidor da óxido nítrico sintase. Unitermos:Dapsona. Metemoglobinemia. L-arginina. Óxido nítrico. L-NAME. INTRODUCTIONDapsone (4,4'-diaminodiphenylsulfone, DDS) is a potent antibacterial and anti-inflammatory compound and has been clinically used in the treatment of leprosy as a component of a multidrug therapy that includes a combination of DDS, clofazimine and rifampicin (Katoch 2002;Walker, Lockwood 2007). The drug is also used for the treatment of malaria and Pneumocystic carinii pneumonia in patients with acquired immunodeficiencysyndrome (Powell et al., 1...

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Effects of H2-receptor antagonists on dapsone-induced methaemoglobinaemia in rats

Cited by 8 publications

References 22 publications

The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats

The effect of ethyl pyruvate on dapsone-induced methemoglobinemia in rats

Sometimes, It’s Just Black and White: Dark Urine and Pallor in a 2-Year-Old Boy

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

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