Evaluation of the Combined Effect of Artemisinin and Ferroptosis Inducer RSL3 against Toxoplasma gondii.
Int J Mol Sci
; 24(1)2022 Dec 23.
Article
em En
| MEDLINE
| ID: mdl-36613672
ABSTRACT
Toxoplasma gondii is a widespread intracellular pathogen that infects humans and a variety of animals. Dihydroartemisinin (DHA), an effective anti-malarial drug, has potential anti-T. gondii activity that induces ferroptosis in tumor cells, but the mechanism by which it kills T. gondii is not fully understood. In this study, the mechanism of DHA inhibiting T. gondii growth and its possible drug combinations are described. DHA potently inhibited T. gondii with a half-maximal effective concentration (EC50) of 0.22 µM. DHA significantly increased the ROS level of parasites and decreased the mitochondrial membrane potential, which could be reversed by ferroptosis inhibitors (DFO). Moreover, the ferroptosis inducer RSL3 inhibited T. gondii with an EC50 of 0.75 µM. In addition, RSL3 enhanced the DHA-induced ROS level, and the combination of DHA and RSL3 significantly increased the anti-Toxoplasma effect as compared to DHA alone. In summary, we found that DHA-induced ROS accumulation in tachyzoites may be an important cause of T. gondii growth inhibition. Furthermore, we found that the combination of DHA and RSL3 may be an alternative to toxoplasmosis. These results will provide a new strategy for anti-Toxoplasma drug screening and clinical medication guidance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxoplasma
/
Toxoplasmose
/
Artemisininas
/
Ferroptose
Tipo de estudo:
Guideline
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article