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Plasmodium berghei: Implication of Intracellular Glutathione and Its Related Enzyme in Chloroquine Resistance in Vivo

Identifieur interne : 002B45 ( Main/Exploration ); précédent : 002B44; suivant : 002B46

Plasmodium berghei: Implication of Intracellular Glutathione and Its Related Enzyme in Chloroquine Resistance in Vivo

Auteurs : V. L. Dubois [France] ; D. F. N. Platel [France] ; G. Pauly [France] ; J. Tribouleyduret [France]

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RBID : ISTEX:CC09C9FC0F0BE631DD888F853A858282EEE03360

Abstract

Abstract: Glutathione (GSH) plays a critical role in the detoxication and the protection of cells against oxidative stress. In the present study we examined the relationship between the intracellular GSH level as well as glutathione S-transferase (GST), glutathione reductase (GR), and glutathione 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 increases in GSH levels and GST activity within resistant parasites were observed, compared to sensitive parasites. On the other hand, GR and GPx activities 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 depletion 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 altered GSH and GST levels and activity, respectively, which enable the detoxification of chloroquine in resistant parasites.

Url:
DOI: 10.1006/expr.1995.1099


Affiliations:


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