Mukhopadhyay R, Madhubala R
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Biochem Pharmacol. 1994 Feb 11;47(4):611-5. doi: 10.1016/0006-2952(94)90122-8.
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.
丁基羟基茴香醚(BHA)、视黄酸(RA)、醋酸视黄醇(RAc)和亚硒酸钠(Na2SeO3)可抑制杜氏利什曼原虫前鞭毛体(菌株UR6和AG83)的生长。两种菌株的前鞭毛体生长均呈现剂量依赖性抑制。对于UR6菌株,抑制生长速率50%所需的BHA、RA/RAc和Na2SeO3浓度分别为0.5微克/毫升、0.5微摩尔和0.125毫摩尔。对于AG83菌株,BHA的半数致死剂量(LD50)为1微克/毫升,而RA/RAc和Na2SeO3的LD50与UR6菌株相同。在利什曼原虫属中,生长似乎与多胺生物合成有关并依赖于多胺生物合成(Bachrach U等人,《实验寄生虫学》48: 457 - 463,1979)。测试这些抗利什曼原虫药物通过阻断多胺生物合成发挥抑制作用可能性的实验表明,鸟氨酸脱羧酶活性降低和多胺水平受到抑制可能是BHA和RA抑制前鞭毛体生长的一种机制。