Therapeutic effect of ascorbic acid on dapsone-induced methemoglobinemia in rats

Abstract

ObjectiveDapsone (diaminodiphenyl sulfone, DDS) is currently used to treat leprosy, malaria, dermatitis herpetiformis, and other diseases. It is also used to treat pneumocystis pneumonia and Toxoplasma gondii infection in HIV-positive patients. The most common adverse effect of DDS is methemoglobinemia from oxidative stress. Ascorbic acid is an antioxidant and reducing agent that scavenges the free radicals produced by oxidative stress. The present study aimed to investigate the effect of ascorbic acid in the treatment of DDS induced methemoglobinemia.MethodsMale Sprague-Dawley rats were divided into three groups: an ascorbic acid group, a methylene blue (MB) group, and a control group. After DDS (40 mg/kg) treatment via oral gavage, ascorbic acid (15 mg/kg), MB (1 mg/kg), or normal saline were administered via tail vein injection. Depending on the duration of the DDS treatment, blood methemoglobin levels, as well as the nitric oxide levels and catalase activity, were measured at 60, 120, or 180 minutes after DDS administration.ResultsMethemoglobin concentrations in the ascorbic acid and MB groups were significantly lower compared to those in the control group across multiple time points. The plasma nitric oxide levels and catalase activity were not different among the groups or time points.ConclusionIntravenous ascorbic acid administration is effective in treating DDS-induced methemoglobinemia in a murine model.

Ascorbic Acid for Methemoglobinemia Treatment: A Case Report and Literature Review

“…A prospective study conducted in rats compared single doses of ascorbic acid 15 mg/kg administered over 5 minutes, methylene blue 1 mg/kg, and placebo, and found a decrease in methemoglobin at 180 minutes in methylene blue (4.8%) and ascorbic acid (10%) compared with placebo (20.4%). 17 The authors concluded that while ascorbic acid was effective, it was not as effective as methylene blue and proposed that a higher dose might be required to achieve a similar decrease in methemoglobin levels. Our case report utilized a total dose of 8000 mg (116 mg/kg), which is significantly higher than the previously mentioned prospective study.…”

Methaemoglobinaemia in pregnancy: Real world experience in a single centre in Malaysia

“…For moderate-to-severe forms, ascorbic acid, which prevents haemoglobin conversion to methaemoglobin due to its antioxidant effects, as well as methylene blue are recommended, particularly in symptomatic cases with methaemoglobin levels above 20%. 3,6,7 In our series, methylene blue was administered in one pregnancy during emergency LSCS due to symptomatic presentation with methaemoglobin level above 40%. The teratogenic risk of methylene blue is negligible in this case as baby was delivered soon after its administration, consistent with a reported case.…”

Challenges in Managing a Lepromatous Leprosy Patient Complicated with Melioidosis Infection, Dapsone-Induced Methemoglobinemia, Hemolytic Anemia, and Lepra Reaction

“…Methylene blue is reduced to leukomethylene blue, which acts as an artificial electron donor to methemoglobin, thereby enhancing the ability of erythrocytes to reduce methemoglobin. Vitamin C has antioxidant effects on hemoglobin to prevent conversion to methemoglobin [ 2 , 3 ]. Our patient responded well to methylene blue and vitamin C, as evidenced by the increment in oxygen saturation as well as complete resolution of methemoglobinemia and hemolysis.…”