The effects of ascorbate-induced free radicals on Plasmodium falciparum.
Ascorbic acid has been shown to cause stage-dependent effects on the in vitro development of Plasmodium falciparum. While vitamin C marginally enhanced the development of young parasites, it proved highly destructive to the advanced forms. The present study evaluates the mechanisms by which vitamin C affects the parasite. The treatment of parasitized erythrocytes with ascorbate resulted in the conversion of added salicylate to dihydroxybenzoate products, indicating the involvement of hydroxyl radicals. There was a stage specific sensitivity, increasing conversion with progressing parasite development. This specificity could not be attributed to the altered uptake of salicylate by the parasitized erythrocyte, since salicylate uptake was similar in either parasitized or non-parasitized erythrocytes. In distinction, increased uptake of ascorbate by parasitized erythrocytes could account for an elevated oxidant stress. The treatment with ascorbate also caused the oxidation of hemoglobin to methemoglobin and the peroxidation of membrane lipids. Added catalase markedly inhibited the ascorbate-induced effects on parasite development. "Free" plasmodia were also vulnerable to treatment with ascorbate like the parasites within their host cells. These results are in accord with a free radical mechanism of damage to the infected erythrocytes. During the growth of P. falciparum the infected erythrocytes release increasing levels of iron-containing structures that are redox-active and can catalyze the formation of highly reactive oxygen derived species. The findings also indicate the multiplicity of the mode of action of ascorbate on the host-parasite system.
Marva
E
E
Department of Parasitology, Hebrew University, Jerusalem, Israel.
Golenser
J
J
Cohen
A
A
Kitrossky
N
N
Har-el
R
R
Chevion
M
M
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology*; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism*; D062385:Hydroxybenzoates / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008706:Methemoglobin / Q000032:analysis; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum / Q000187:drug effects*; D013045:Species Specificity
D005609:Free Radicals; D006878:Hydroxides; D062385:Hydroxybenzoates; D008315:Malondialdehyde; C009135:2,3-dihydroxybenzoic acid; D008706:Methemoglobin; D001205:Ascorbic Acid