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

Malaria Journal

Research

Camille Desgrouas¹  Bruno Pradines²  Jérome Dormoi²  Sébastien Briolant³ 

[1] UMR MD3, Aix Marseille Université, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France;Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France;Direction Interarmées du Service de Santé, Cayenne, Guyane;Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, Guyane;

关键词: Malaria;    Plasmodium;    Anti-malarial drug;    in vivo;    Resistance;    Methylene blue;    Atorvastatin;   

DOI  :  10.1186/1475-2875-12-127

 received in 2013-03-01, accepted in 2013-04-10,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Dormoi et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.