Abstract | BACKGROUND: OBJECTIVES: This 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. RESULTS: AVA 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. CONCLUSIONS: The 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.
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Authors | Jérôme Dormoi, Sébastien Briolant, Aurélie Pascual, Camille Desgrouas, Christelle Travaillé, Bruno Pradines |
Journal | Malaria journal
(Malar J)
Vol. 12
Pg. 302
(Aug 30 2013)
ISSN: 1475-2875 [Electronic] England |
PMID | 23988087
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- Antimalarials
- Artemisinins
- Biomarkers
- Heptanoic Acids
- Pyrroles
- artenimol
- Atorvastatin
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Topics |
- Animals
- Anti-Inflammatory Agents
(administration & dosage)
- Antimalarials
(administration & dosage)
- Artemisinins
(administration & dosage)
- Atorvastatin
- Biomarkers
(analysis)
- Disease Models, Animal
- Drug Therapy, Combination
(methods)
- Female
- Heptanoic Acids
(administration & dosage)
- Inflammation
(pathology)
- Malaria, Cerebral
(drug therapy, pathology)
- Mice
- Mice, Inbred C57BL
- Pyrroles
(administration & dosage)
- Survival Analysis
- Treatment Outcome
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