Role of angiotensin pathway and its target therapy to rescue from experimental cerebral malaria.
Microbes Infect
; 26(4): 105333, 2024.
Article
de En
| MEDLINE
| ID: mdl-38570086
ABSTRACT
Cerebral malaria (CM) induced by Plasmodium falciparum is a devastating neurological complication that may lead the patient to coma and death. This study aimed to protect Plasmodium-infected C57BL6 mice from CM by targeting the angiotensin II type 1 (AT1) receptor, which is considered the common connecting link between hypertension and CM. In CM, AT-1 mediates blood-brain barrier (BBB) damage through the overexpression of ß-catenin. The AT-1-inhibiting drugs, such as irbesartan and losartan, were evaluated for the prevention of CM. The effectiveness of these drugs was determined by the down regulation of ß-catenin, TCF, LEF, ICAM-1, and VCAM-1 in the drug-treated groups. The expression levels of VE-cadherin and vinculin, essential for the maintenance of BBB integrity, were found to be restored in the drug-treated groups. The pro-inflammatory cytokine levels were decreased, and the anti-inflammatory cytokine levels increased with the treatment. As a major highlight, the mean survival time of treated mice was found to be increased even in the absence of treatment with an anti-malarial agent. The combination of irbesartan or losartan with the anti-malarial agent α/ß-arteether has contributed to an 80% cure rate, which is higher than the 60% cure rate observed with α/ß-arteether alone treatment.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Paludisme cérébral
/
Modèles animaux de maladie humaine
/
Irbésartan
/
Souris de lignée C57BL
Limites:
Animals
Langue:
En
Journal:
Microbes Infect
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
MICROBIOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Inde