PLASMODIUM-BERGHEI - IMPLICATION OF INTRACELLULAR GLUTATHIONE AND ITSRELATED ENZYME IN CHLOROQUINE RESISTANCE IN-VIVO

Glutathione (GSH) plays a critical role in the detoxication and the pr otection of cells against oxidative stress. In the present study we ex amined the relationship between the intracellular GSH level as well as glutathione S-transferase (GST), glutathione reductase (GR), and glut athione peroxidase (GPx) activities and how they relate to Plasmodium berghei resistance to chloroquine. Resistant strains (CQR30 and CQR60) were selected in vivo from a sensitive strain (NK65). Marked increase s in GSH levels and GST activity within resistant parasites were obser ved, compared to sensitive parasites. On the other hand, GR and GPx ac tivities were similar in sensitive and resistant parasites. Treatment with chloroquine did not influence the intracellular level of GSH, but it was found to significantly decrease GR activity. Intracellular dep letion of GSH, by a nontoxic concentration of buthionine sulfoximine ( BSO), significantly sensitized the resistant parasites to chloroquine. These results suggest that the P. berghei resistance results from alt ered GSH and GST levels and activity, respectively, which enable the d etoxification of chloroquine in resistant parasites. (C) 1995 Academic Press, Inc.