Inhibition of the intraerythrocytic development of Plasmodium falciparum in glucose-6-phosphate dehydrogenase deficient erythrocytes is enhanced by oxidants and by crisis form factor.
In this study, we have examined P. falciparum development in untreated normal or G6PD deficient erythrocytes as well as in parasitized cells exposed to isouramil--a fava bean extract known to induce oxidant stress in G6PD deficient erythrocytes (a condition known as favism), to diamide--a thiol oxidizing agent and to crisis form factor (CFF)--a non-immunoglobulin product found in the sera of man immune to malaria. We observed a significant retardation in intraerythrocytic development of parasites cultured in the G6PD deficient cells in comparison with parasites grown in the normal ones. Plasmodia within the G6PD deficient erythrocytes were markedly more sensitive to the inhibitory activity of CFF or the oxidizing agents diamide and isouramil. Mature stages of the parasites in both normal and G6PD deficient erythrocytes were more vulnerable than young ring forms, to oxidizing agents. The overall results show that the genetic trait of the host cell and the degree of maturation of the plasmodia are both crucial factors in determining the sensitivity of the parasite to oxidant stress.
Golenser
J
J
Department of Parasitology, S. F. Kuvin Centre for the Study of Infectious and Tropical Diseases, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Miller
J
J
Spira
D T
DT
Kosower
N S
NS
Vande Waa
J A
JA
Jensen
J B
JB
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology; D002478:Cells, Cultured; D003958:Diamide / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000469:parasitology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*
D001463:Barbiturates; D001685:Biological Factors; D003958:Diamide; C032211:isouramil