Inhibition of glutathione synthesis of Ascaris suum by buthionine sulfoximine.
We investigated the effect of DL-buthionine-S,R-sulfoximine (BSO), a selective glutathione (GSH)-depleting agent, on the GSH synthesis of Ascaris suum. The GSH concentrations of the reproductive and muscle tissues of A. suum were determined to be 8.5 +/- 0.3 and 14.3 +/- 1.3 (n = 3) nmol/mg protein, respectively. After treatment of the parasites with 10 microM BSO for 24 h, the GSH content of the reproductive tissue of A. suum was totally depleted as compared with that of untreated controls. However, the GSH levels of the muscle tissue were reduced to only 50% after treatment of the worms for 24 h with 10 microM BSO. Exogenous GSH had no significant effect on the GSH level of the parasites when the worms were incubated for 4 h in RPMI 1640 medium supplemented with 1 mM GSH. In the presence of exogenous GSH, BSO was less effective in depleting the GSH levels of the parasites, which may indicate that the parasites can replenish their GSH levels. GSH depletion, which has been discussed as being therapeutically effective when normal and tumor cells or parasites have markedly different requirements for GSH, may have applications in the development of drugs against nematode infections.
Hussein
A S
AS
Department of Biochemical Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Walter
R D
RD
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D000969:Antinematodal Agents / Q000494:pharmacology*; D017165:Ascaris suum / Q000187:drug effects / Q000378:metabolism*; D019328:Buthionine Sulfoximine; D005835:Genitalia / Q000201:enzymology; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009132:Muscles / Q000201:enzymology; D009928:Organ Specificity; D013997:Time Factors
D000963:Antimetabolites; D000969:Antinematodal Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione