Effect of dihydroartemisinin on the antioxidant capacity of P. falciparum-infected erythrocytes.
Many lines of evidence reveal that artemisinin, an antimalarial containing endoperoxide, generates free radicals to kill malaria parasites. The present study re-evaluated the antioxidants of P. falciparum-infected erythrocytes in the absence and presence of 0.25, 0.5 and 1.0 ng/ml of dihydroartemisinin (DHA), the active metabolite of artemisinin. The ratio of reduced to oxidized glutathione (GSH/GSSG) and activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were determined. The data indicated that malaria infection induced oxidative stress in erythrocytes that resulted in a significant lower GSH in parasitized cells compared to the non-parasitized. DHA showed no effect on the antioxidant levels of non-parasitized erythrocytes treated under similar conditions as P. falciparum-infected erythrocytes. However, significantly lower GSH as well as catalase and GPx activities in parasitized cells were seen at drug concentrations of 0.5 and 1.0 ng/ml (p < 0.05). GSH is the most sensitive indicator of oxidative stress in malaria-infected erythrocytes both in the absence and in the presence of DHA. Parasite GPx might play a more important role than catalase in the elimination of peroxide. Parasite viabilities in the presence of DHA were analyzed simultaneously and were affected to a greater extent than the antioxidant levels. The present observation showed that although DHA killed malaria parasites by generating free radicals from the endoperoxide bridge causing the reduction of antioxidants, but the depletion of parasite antioxidants is not a prerequisite for the parasite death.
Ittarat
Wanida
W
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. mtwit@mahidol.ac.th
Sreepian
Apichai
A
Srisarin
Apapan
A
Pathepchotivong
Kritsana
K
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D037621:Artemisinins / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*; D016019:Survival Analysis
D000962:Antimalarials; D000975:Antioxidants; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol; D005979:Glutathione Peroxidase