Graphical abstractT. cruzi II strains accumulate more 8-oxoguanine in the kDNA after hydrogen peroxide-induced 18 oxidative stress than T. cruzi I strains. NT: untreated; T: treated.Research highlights▶ Distinct levels of DNA mismatch repair activity are found among T. cruzi strains. ▶ In T. cruzi and T. brucei, MSH2 has a mitochondrial function involved in the response to oxidative stress.

Trypanosoma cruzi antioxidant enzymes are among the factors that guarantee parasite survival and maintain infection, enabling T. cruzi to cope with oxidative stress. Herein, the expression of cytosolic (TcCPx) and mitochondrial (TcMPx) tryparedoxin peroxidases was evaluated in tissue culture-derived trypomastigotes upon incubation with different concentrations of H(2)O(2). TcCPx expression slightly increased (5.4%) in cells submitted to 10 μM H(2)O(2) treatment when compared to the control, but decreased when higher H(2)O(2) concentrations (20-50 μM) were employed. Under these conditions, TcMPx expression increased (∼53%) with 10 μM-treatment compared to the control, followed by a reduction that reached ∼46% of the control when using the highest concentration tested. Interestingly, in the supernatant of the incubations, TcCPx, but not TcMPx, was detected, and its levels increased concomitantly with its decreased expression in the intracellular compartment. Our data show that peroxiredoxins in the tissue culture-derived trypomastigote can be modulated under oxidative stress and are present in higher amounts when compared to the epimastigote stage of T. cruzi. Additionally, due to the different expression patterns observed upon H(2)O(2)-treatment, each peroxiredoxin may play a distinct role in protecting the parasite under oxidative stress conditions.

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Understanding the energy-transduction pathways employed by Trypanosoma cruzi, the etiological agent of Chagas disease, may lead to the identification of new targets for development of a more effective therapy. Herein, the contribution of different substrates for O(2) consumption rates along T. cruzi epimastigotes (Tulahuen 2 and Y strains) growth curve was evaluated. O(2) consumption rates were higher at the late stationary phase not due to an increase on succinate-dehydrogenase activity. Antimycin A and cyanide did not totally inhibit the mitochondrial respiratory chain (MRC). Malonate at 10 or 25 mM was not a potent inhibitor of complex II. Comparing complex II and III, the former appears to be the primary site of H(2)O(2) release. An update on T. cruzi MRC is presented that together with our results bring important data towards the understanding of the parasite's MRC. The findings mainly at the stationary phase could be relevant for epimastigotes transformation into the metacyclic form, and in this sense deserves further attention.

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Cadmium is a heavy metal of increasing environmental concern that has long been associated to several human pathological processes. Recent population surveys have correlated cadmium non-occupational exposure to widespread idiopathic pathologies. Food and tobacco are reported to be the main exposure sources of cadmium to the general population, as phosphate fertilizers are rich in such a metal, thus contaminating the crops. Although its mechanisms of toxicity are not a consensus in the literature, it is well established that reactive oxygen species play a key role in this process, leading to the oxidation of several biological molecules. We have therefore assessed whether three environmentally realistic doses of cadmium alter the oxidative status of Wistar rat testis and eventually result in histological damages. Our results show that even the lowest environmental dose of cadmium was able to disturb the endogenous antioxidant system in Wistar testis, although an increase in lipid peroxidation was observed only within the group exposed to the highest environmental dose. Despite that no remarkable morphological changes were observed in any group, significant alterations in blood vessel lumen were reported for some cadmium-exposed animals, suggesting that endothelium is one of the primary targets involved in cadmium toxicity.

S U M M A R YThe infectivity and virulence of pathogenic trypanosomatids are directly associated with the efficacy of their antioxidant system. Among the molecules involved in the trypanosomatid response to reactive oxygen or nitrogen species, trypanothione reductase (TRed) is a key enzyme. In this study, we performed a molecular and functional characterization of the TRed enzyme from Trypanosoma rangeli (TrTRed), an avirulent trypanosome of mammals. The TrTRed gene has an open reading frame (ORF) of 1473 bp (∼490 aa, 53 kDa) and occurs as a single-copy gene in the haploid genome. The predicted protein contains two oxidoreductase domains, which are equally expressed in the cytosol of epimastigotes and trypomastigotes. Nicotinamide adenine dinucleotide phosphate (NADPH) generation is reduced and endogenous H 2 O 2 production is elevated in T. rangeli Choachí strain compared with T. cruzi Y strain epimastigotes. Oxidative stress induced by H 2 O 2 does not induce significant alterations in TrTRed expression. Overexpression of TrTRed did not influence in vitro growth or differentiation into trypomastigotes, but mutant parasites showed increased resistance to H 2 O 2 -induced stress. Our results indicate that T. rangeli constitutively expresses TRed during the entire life cycle, with reduced levels during infective and non-replicative trypomastigote stages.