Antiproliferative effect of sera from chagasic patients on Trypanosoma cruzi epimastigotes. Involvement of xanthine oxidase.

Serum from asymptomatic or symptomatic (with cardiovascular manifestations) chagasic patients depleted of the complement system displayed an antiproliferative effect on Trypanosoma cruzi epimastigotes, RA strain, when added to the growth medium. This effect was also observed when patient's serum was depleted of specific antibodies. The antiproliferative effect was both time and concentration dependent. It was confined to the non-dialyzable, high molecular weight, fraction of the serum. This effect was abrogated by allopurinol and catalase, and enhanced by N-ethylmaleimide. Xanthine oxidoreductase and xanthine oxidase activities were increased in the chagasic sera, while catalase activity remained unchanged. Parasites exposed to chagasic sera showed a decrease in Fe/superoxide dismutase activity as well as an increase in membrane lipoperoxidation. Our data provides evidence to support the idea that the antiproliferative activity observed in sera from chagasic patients may be due, at least partially, to a direct effect of hydrogen peroxide on the epimastigotes of T. cruzi. The increase of hydrogen peroxide to antiproliferative levels might result from an increase in xanthine oxidase activity in the serum of patients infected with the parasite.

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.