Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model

Malaria Journal

Research

Raoulin Soulard¹  Joel Mosnier²  Rémy Amalvict³  Eric Baret³  Christophe Rogier³  Sébastien Briolant³  Bruno Pradines³  Jérome Dormoi³  Jean-Baptiste Souraud⁴  Hélène Savini⁵ 

[1] Service d'Anatomie et Cytologie Pathologiques, Hôpital d'Instruction des Armées Saint-Anne, Toulon, France;Service de Biochimie, Hôpital d'Instruction des Armées Laveran, Marseille, France;Unité de Chirurgie et Physiologie Expérimentale, Institut de Recherche Biomédicale des Armées, Marseille, France;Unité de parasitologie, Unité de recherche sur les maladies infectieuses et transmissibles émergentes - UMR 6236, Institut de recherche biomédicale des armées - antenne de Marseille, Allée du Médecin-colonel Jamot, Parc le Pharo, BP 60109, 13262, Marseille Cedex 7, France;Unité de parasitologie, Unité de recherche sur les maladies infectieuses et transmissibles émergentes - UMR 6236, Institut de recherche biomédicale des armées - antenne de Marseille, Allée du Médecin-colonel Jamot, Parc le Pharo, BP 60109, 13262, Marseille Cedex 7, France;Service d'Anatomie et Cytologie Pathologiques, Hôpital d'Instruction des Armées Saint-Anne, Toulon, France;Unité de parasitologie, Unité de recherche sur les maladies infectieuses et transmissibles émergentes - UMR 6236, Institut de recherche biomédicale des armées - antenne de Marseille, Allée du Médecin-colonel Jamot, Parc le Pharo, BP 60109, 13262, Marseille Cedex 7, France;Service de Maladies Infectieuses, Hôpital d'Instruction des Armées Laveran, Marseille, France;

关键词: Atorvastatin;    Mefloquine;    Pentoxifylline;    Cerebral Malaria;    Apoptotic Neuron;   

DOI  :  10.1186/1475-2875-11-13

 received in 2011-09-20, accepted in 2012-01-10,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundOne of the major complications of Plasmodium falciparum infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine.MethodsThe efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining.ResultsAVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown.ConclusionsThe combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.

【 授权许可】

Unknown   
© Souraud et al; licensee BioMed Central Ltd. 2012. 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.