Inhibition of glutathione synthesis as a chemotherapeutic strategy for leishmaniasis.
This study focuses on the use of buthionine sulphoximine (BSO), a gamma-glutamylcysteine synthetase inhibitor, on Leishmania donovani growth. The effect of BSO on amastigote multiplication within macrophages showed that 5 mM 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.
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
P
P
Kapoor
M
M
Sachdev
R
R
Madhubala
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000096:biosynthesis; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008647:Mesocricetus; D051379:Mice
D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione