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

Autor: Christophe Rogier, Raoulin Soulard, Joel Mosnier, Sébastien Briolant, Jérôme Dormoi, Eric Baret, Hélène Savini, Rémy Amalvict, Jean-Baptiste Souraud, Bruno Pradines
Přispěvatelé: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et Cytologie Pathologiques, Hôpital d'Instruction des Armées Saint-Anne, Service de Biochimie, Hôpital d'instruction des armées Laveran, Unité de Chirurgie et Physiologie Expérimentale, Institut de Recherche Biomédicale des Armées (IRBA), Service de Maladies Infectieuses, This work was supported by the Direction Centrale du Service de Santé des Armées and the Délégation Générale pour l'Armement (grant 10co405)., Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
MESH: Histocytochemistry
Plasmodium berghei
Atorvastatin
[SDV]Life Sciences [q-bio]
MESH: Neurons
Apoptosis
Pharmacology
Mice
Medicine
MESH: Animals
MESH: Treatment Outcome
Neurons
0303 health sciences
Quinine
biology
Histocytochemistry
Mefloquine
Brain
Immunohistochemistry
3. Good health
Treatment Outcome
Infectious Diseases
Cerebral Malaria
MESH: Survival Analysis
MESH: Pyrroles
Drug Therapy
Combination
Female
MESH: Mefloquine
medicine.drug
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
MESH: Heptanoic Acids
Malaria
Cerebral
Neuroprotection
lcsh:Infectious and parasitic diseases
Sepsis
MESH: Malaria
Cerebral
Antimalarials
03 medical and health sciences
MESH: Brain
In vivo
parasitic diseases
Animals
MESH: Plasmodium berghei
lcsh:RC109-216
Pyrroles
MESH: Mice
030304 developmental biology
030306 microbiology
business.industry
Research
MESH: Apoptosis
MESH: Immunohistochemistry
medicine.disease
biology.organism_classification
Survival Analysis
MESH: Antimalarials
Disease Models
Animal
MESH: Drug Therapy
Combination
Heptanoic Acids
Immunology
Parasitology
MESH: Disease Models
Animal
business
MESH: Female
Zdroj: Malaria Journal
Malaria Journal, BioMed Central, 2012, 11, pp.13. ⟨10.1186/1475-2875-11-13⟩
Malaria Journal, 2012, 11, pp.13. ⟨10.1186/1475-2875-11-13⟩
Malaria Journal, Vol 11, Iss 1, p 13 (2012)
ISSN: 1475-2875
DOI: 10.1186/1475-2875-11-13⟩
Popis: 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.
Databáze: OpenAIRE
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