Polyamines as a defense mechanism against lipoperoxidation in Trypanosoma cruzi

Abstract

The polyamines, spermine and spermidine – small organic polycations that are absolutely required for eukaryotic cell growth – are shown here to function in Trypanosoma cruzi epimastigotes, as protectors of membrane lipoperoxidation by reactive oxygen species generated either by H 2O 2/Fe 2+ or nifurtimox. In vitro, spermine and spermidine inhibited lipoperoxidation in a dose dependent manner. Spermine was more efficient than spermidine in its inhibitory effect. Lipid peroxidation induced by H 2O 2 showed an IC 50 of 0.55 mM for spermine and 0.9 mM for spermidine while an IC 50 of 0.8 mM for spermine and 1.5 mM for spermidine were observed when lipoperoxidation was elicited by nifurtimox. Likewise in vivo, both exogenously added spermine and spermidine or endogenous increase of spermine levels induced by phorbol ester, protected against lipoperoxidation and decreased citotoxicity provoked by nifurtimox. Putrescine and cadaverine, also present in T. cruzi had no effect at all. None of the polyamines had any effect neither on the scavenging of superoxide anion nor on the regulation of antioxidant enzymes such as superoxide dismutase and peroxidases involved in H 2O 2 detoxification. Here we point out that spermine, by acting as a protector of membrane lipoperoxidation might contribute to survival of T. cruzi continuously exposed to oxidative stress.