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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

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

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Jean-Baptiste Souraud, Sébastien Briolant, Jérome Dormoi, Joel Mosnier, Hélène Savini, Eric Baret, Rémy Amalvict, Raoulin Soulard, Christophe Rogier, Bruno Pradines
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-13) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

JBS, SB, JD conceived, designed, performed the in vivo experiments and drafted the manuscript. JM, EB, RA, HS, NT, RS participated in experiments. BP and CR conceived, designed and coordinated the study and drafted the manuscript. All authors read and approved the final manuscript.

Abstract

Background

One 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.

Methods

The 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.

Results

AVA 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.

Conclusions

The 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.
Zusatzmaterial
Authors’ original file for figure 1
12936_2011_1967_MOESM1_ESM.ppt
Authors’ original file for figure 2
12936_2011_1967_MOESM2_ESM.pdf
Authors’ original file for figure 3
12936_2011_1967_MOESM3_ESM.pdf
Authors’ original file for figure 4
12936_2011_1967_MOESM4_ESM.ppt
Literatur
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