Curcumin could prevent methemoglobinemia induced by dapsone in rats

Bergamaschi, Mateus M.; Alcantara, Greyce Kelly Steinhorst; Valério, Daniel Augusto Rodrigues; Queiróz, Regina Helena Costa

doi:10.1016/j.fct.2011.03.025

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…The dose of 40 mg/kg (i.p.) of DDS was known to produce methemoglobinemia in rats based on previous studies by our group (Malfara et al, 2002;De Moraes et al, 2008;Bergamaschi et al, 2011). When ARG was administered in a single dose two hours prior to DDS (40 mg/kg) it failed to reduce DDS-induced methemoglobinemia (Figure 1).…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

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

Moraes

Bergamaschi

Bianchi

et al. 2012

Braz. J. Pharm. Sci.

Self Cite

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“…We believe that the biochemical effect of curcuminoids and their analogs is not only due to the phenolic hydroxyl group, but is also associated with the number of free -OH groups on the benzene ring as shown in Figure 1. Collectively, there is a possibility of using the modified analogs as supplement for human diseases (Gupta et al, 2012;Bergamaschi et al, 2011). However, additional studies are needed to elucidate this finding into the realm of clinical management of G6PD-deficient patients.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2016

j.appsci

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency can cause hemolytic anemia in response to oxidative stress. This study was undertaken to study the protective effect of natural curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) with curcuminoid analogs (di-O-demethylcurcumin and mono-O-demethylcurcumin) in healthy and G6PDdeficient red blood cells. After pretreatment blood with the test compounds, 0.75 mM sodium nitrite-oxidized hemolysate was determined for methemoglobin (metHb) formation. Concurrently, the released hemoglobin from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-challenged cells was measured for hemolysis. We found that most of the compounds reduced metHb formation and oxidative hemolysis in red cells. After pretreatment with curcuminoid analogs, the oxidized hemoglobins were lower than treated with natural compounds. Furthermore, this study showed that demethylcurcumin analogs certainly protect AAPH-induced red cell lysis. This study can be concluded that curcuminoid analogs with different phenol rings possibly have higher antioxidant activity in order to protect the oxidative stress condition, especially in G6PD deficiency.

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“…A study conducted in rats demonstrated that pretreatment with curcumin (both single dose and multiple doses) was able to prevent the methemoglobinemia associated with exposure to the antimycobacterial drug dapsone. 143 Curcumin is able to significantly reduce the incidence of abnormal oro-facial movements in rats treated with the dopamine D2 receptor antagonist haloperidol, and a proteomic analysis revealed that this effect was correlated with an increase in the translational expression of Bcl-x L . 144 A recent study demonstrated that curcumin may exert chemopreventative potential in cases of oxidative/nitrative stress following praziquantel treatment of liver fluke infections.…”

Section: Toxicologymentioning

confidence: 98%

Pharmacological and clinical properties of curcumin

Beevers¹,

Huang

2011

BTAT

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The polyphenol natural product curcumin has been the subject of numerous studies over the past decades, which have identified and characterized the compound's pharmacokinetic, pharmacodynamic, and clinical pharmacological properties. In in vitro and in vivo model systems, curcumin displays potent pharmacological effects, by targeting many critical cellular factors, through a diverse array of mechanisms of action. Despite this tremendous molecular versatility, however, the clinical application of curcumin remains limited due to poor pharmacokinetic characteristics in human beings. The current trend is to develop and utilize unique delivery systems, chemical derivatives, and chemical analogs to circumvent these pharmacological obstacles, in order to optimize the conditions for curcumin as a chemopreventive and chemotherapeutic agent in diseases such as cancer, diabetes, obesity, Alzheimer's disease, and inflammatory disorders. The present work seeks to review recent studies in the basic pharmacological principles and potential clinical applications of curcumin.

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Curcumin could prevent methemoglobinemia induced by dapsone in rats

Cited by 6 publications

References 34 publications

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

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

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Pharmacological and clinical properties of curcumin

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