Polyamines as a defense mechanism against lipoperoxidation in Trypanosoma cruzi.
The polyamines, spermine and spermidine--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 H2O2/Fe2+ 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 H2O2 showed an IC50 of 0.55 mM for spermine and 0.9 mM for spermidine while an IC50 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 H2O2 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.
School of Medicine, Universidad Abierta Interamericana (UAI), Buenos Aires, Argentina.
Susana M
SM
Hernández
Marcela S
MS
Sánchez
Martha N Schwarcz
MN
de Tarlovsky
D000818:Animals; D002103:Cadaverine / Q000494:pharmacology; D002462:Cell Membrane; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D009547:Nifurtimox / Q000494:pharmacology; D011700:Putrescine / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013095:Spermidine / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism*
D017382:Reactive Oxygen Species; D013096:Spermine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D002103:Cadaverine; D009547:Nifurtimox; D013095:Spermidine; D011700:Putrescine