Effect of antioxidants on the growth and polyamine levels of Leishmania donovani.

Butylated hydroxyanisole (BHA), retinoic acid (RA), retinol acetate (RAc) and sodium selenite (Na2SeO3) inhibited the growth of Leishmania donovani promastigotes (strains UR6 and AG83). There is a dose dependent inhibition of promastigote growth in both the strains. The concentrations of BHA, RA/RAc and Na2SeO3 required for 50% inhibition of the rate of growth were 0.5 microgram/mL, 0.5 microM and 0.125 mM, respectively, for UR6. In the case of AG83, LD50 for BHA was 1 microgram/mL whereas LD50 for RA/RAc and Na2SeO3 were the same as that of UR6. In Leishmania spp., growth appears to be related to and dependent upon polyamine biosynthesis (Bachrach U et al., Exp Parasitol 48: 457-463, 1979). Experiments to test the possibility that these antileishmanial agents exert their inhibitory effect by blocking polyamine biosynthesis suggest that decrease in ornithine decarboxylase activity and the inhibition of polyamine levels could be a mechanism of inhibition of promastigote growth by BHA and RA.