Improvement of the efficacy of dihydroartemisinin with atorvastatin in an experimental cerebral malaria murine model

Malaria Journal

Research

Christelle Travaillé¹  Camille Desgrouas¹  Bruno Pradines²  Jérôme Dormoi²  Aurélie Pascual²  Sébastien Briolant³ 

[1] UMR MD3, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de Parasitologie, Département d’Infectiologie de Terrain, 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, Département d’Infectiologie de Terrain, 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, France;Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, Guyane, France;

关键词: Malaria;    Plasmodium berghei;    Antimalarial;    Resistance;    In vivo;    Artemisinin;    Statin;   

DOI  :  10.1186/1475-2875-12-302

 received in 2013-04-08, accepted in 2013-08-20,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe medical care of malaria is a clinical emergency because it may develop into severe malaria, which has a high risk of complications and death. One of the major complications of Plasmodium falciparum infections is cerebral malaria (CM), which is responsible for at least 175,000 deaths worldwide each year and has long-term neurological sequelae. Moreover, treatment for CM is only partially effective. Statins are now known to have anti-inflammatory action, to attenuate sepsis and to have neuroprotective effects. In vitro, atorvastatin (AVA) has an anti-malarial activity and has improved the activity of quinine (QN), mefloquine (MQ), and dihydroartemisinin (DHA).ObjectivesThis study had two objectives. First, the ability of AVA to enhance DHA efficacy by improving the survival rate for CM and also decreasing signs of CM was evaluated in a murine model of experimental cerebral malaria (ECM), which was designed in C57BL6/N mice. Second, the inflammatory biomarkers were assessed at D6 and D10 in mice treated by DHA and in untreated mice in which clinical signs of CM appear rapidly and death occurs before D12. Both experiments were designed with seven days of treatment with 40 mg/kg AVA combined with five days of 3 mg/kg DHA administered intraperitoneally.ResultsAVA in combination with DHA in a therapeutic scheme leads to a significant delay in mouse death, and it has an effect on the onset of CM symptoms and on the level of parasitaemia. Evaluation of the biomarkers highlights the significant difference between treated and control mice for five cytokines and chemokines (Eotaxin-CCL11, IL-13, LIX-CXCL5, MIP1b-CCL4 and MIP2) that are known to have a role in chemotaxis.ConclusionsThe combination of DHA and AVA seems to be effective as a therapeutic scheme for improving mouse survival but less effective for cytokine modulation, which is associated with protection against CM. These results call for clinical trials of AVA as an adjuvant with anti-malarial therapy, especially with artemisinin-based combination therapy, in CM treatment or 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.