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

Abstract

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 µ/mL, 0.5 µM and 0.125 mM, respectively, for UR6. In the case of AG83, LD₅₀ for BHA was 1 µg/ 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 Parasitol48: 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.