The in vivo antimalarial activity of methylene blue combined with pyrimethamine, chloroquine and quinine

Garavito, Giovanny; Bertani, Stéphane; Quiliano, Miguel; Valentin, Alexis; Aldana, Ignacio; Deharo, Eric

doi:10.1590/s0074-02762012000600019

Cited by 15 publications

(12 citation statements)

References 24 publications

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“…Several doses of MB were tested to determine the effective dose value; 45 mg/kg/day was found to have the highest potency. This was similar to Garavito et al's [27] findings on MB efficacy on sensitive wild-type P. berghei. Based on this, subsequent tests were carried out using it.…”

Section: Resultssupporting

confidence: 91%

Methylene blue inhibits lumefantrine-resistant Plasmodium berghei

Mwangi

Mumo

Kiboi

et al. 2016

J Infect Dev Ctries

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Introduction: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The largescale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine-and pyrimethamine-resistant strains of P. berghei. Methodology: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. Results: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. Conclusions: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrineand pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine-and pyrimethamine-resistant parasites.

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Section: Resultssupporting

confidence: 91%

Methylene blue inhibits lumefantrine-resistant Plasmodium berghei

Mwangi

Mumo

Kiboi

et al. 2016

J Infect Dev Ctries

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“…Cardamatis wrote in Progrès Médical that he had found MB to be very effective in the early stages of severe malaria cachexia in cases that were resistant to quinine [8]. MB has shown in vitro activity against Plasmodium falciparum strains [9,10] or isolates [11,12] and in vivo activity against Plasmodium vinckei and Plasmodium yoelii parasites [13,14]. …”

Section: Introductionmentioning

confidence: 99%

Impact of methylene blue and atorvastatin combination therapy on the apparition of cerebral malaria in a murine model

Dormoi

Briolant

Desgrouas

et al. 2013

Malar J

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BackgroundProveblue®, a methylene blue dye that complies with European Pharmacopoeia and contains limited organic impurities and heavy metals of recognized toxicity, showed in vitro synergy against Plasmodium falciparum when combined with atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase. The objective of this study was to evaluate the in vivo efficacy of Proveblue® when combined with atorvastatin in a murine model of experimental cerebral malaria.MethodsForty female C57Bl6/N mice were divided into four groups (control, atorvastatin 40 mg/kg for seven days, Proveblue® 10 mg/kg for five days and atorvastatin combined with Proveblue®), infected with Plasmodium berghei ANKA parasites by intraperitoneal inoculation and observed for 45 days.ResultsTreatment with atorvastatin alone did not demonstrate an effect significantly different from no treatment (p = 0.0573). All the mice treated by atorvastatin alone died. Treatment with Proveblue® or a combination of Proveblue® and atorvastatin was significantly increased survival of cerebral malaria (p = 0.0011 and 0.0002, respectively). Although there was only one death in the atorvastatin and Proveblue® combination treatment group (10%) versus two deaths (22%) with Proveblue® treatment, the effect on cerebral malaria was not significant (p = 0.283).ConclusionsThe present work demonstrated, for the first time, the high efficacy of Proveblue® in preventing cerebral malaria. Atorvastatin alone or in combination appears to possess limited use for preventing cerebral malaria. Combination of atorvastatin with lower doses of Proveblue® (<10 mg/kg/day) should be evaluated to show potential synergistic effects in cerebral malaria prevention.

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“…The development of derivatives of 1 exhibiting greater in vivo antimalarial activity would therefore be desirable. In this vein, it is important to keep in mind the possible limitations [46] and slow clearance [47]) and artemisinin derivatives, exemplified by artesunate (recrudescence below 80 mg kg Ϫ1 day Ϫ1 via oral against P. vinckei) (48) are not optimal for treating rodent malaria parasites but are of unquestionable therapeutic value in humans.…”

Section: Discussionmentioning

confidence: 99%