Inhibition of glutathione synthesis as a chemotherapeutic strategy for leishmaniasis
Open Access
- 1 June 2000
- journal article
- research article
- Published by Wiley in Tropical Medicine & International Health
- Vol. 5 (6) , 438-442
- https://doi.org/10.1046/j.1365-3156.2000.00565.x
Abstract
Summary This study focuses on the use of buthionine sulphoximine (BSO), a γ‐glutamylcysteine synthetase inhibitor, on Leishmania donovani growth. The effect of BSO on amastigote multiplication within macrophages showed that 5 m m BSO decreased infectivity by about 50% and the mean number of amastigotes per 100 infected macrophages by 21%. The mechanism may be that BSO resulted in enhanced nitric oxide (NO) levels within macrophages, probably due to inhibition of GSH content since GSH (10 mm) given after BSO treatment led to a decrease in NO compared to macrophages treated with BSO alone which were preexposed to the Leishmania surface molecule lipophosphoglycan.Keywords
This publication has 26 references indexed in Scilit:
- The effect of buthionine sulfoximine on the growth ofLeishmania donovaniin cultureFEMS Microbiology Letters, 1999
- No-induced oxidative stress and glutathione metabolism in rodent and human cellsFree Radical Biology & Medicine, 1996
- Glycoinositolphospholipids of Leishmania major inhibit nitric oxide synthesis and reduce leishmanicidal activity in murine macrophagesEuropean Journal of Immunology, 1995
- Leishmania major‐specific CD8+ T cells are inducers and targets of nitric oxide produced by parasitized macrophagesEuropean Journal of Immunology, 1994
- Pre‐exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activityEuropean Journal of Immunology, 1993
- Nitric oxide: A cytotoxic activated macrophage effector moleculeBiochemical and Biophysical Research Communications, 1988
- Trypanothione: A Novel Bis(glutathionyl)spermidine Cofactor for Glutathione Reductase in TrypanosomatidsScience, 1985
- Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomatidsMolecular and Biochemical Parasitology, 1985
- Selective Modification of Glutathione MetabolismScience, 1983
- Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasis.The Journal of Experimental Medicine, 1981