Francisco et al. Increase of reactive oxygen species by desferrioxamine during experimental Chagas’ disease Figure 3 GT levels in hepatocytes and serum activities of SOD in mice not infected or infected with T. cruzi and not treated or treated with desferrioxamine at days 14 and 21. Significant differences (P < 0.05) between groups are indicated by connecting lines Discussion In the present study, levels of PC were elevated in the IT group (Fig. 1B) suggesting that infection and DFO together increased oxidative stress in the host in order to exert some damage on the parasite. Additionally, the increases in production of TBARS in animals of the INT group that were observed at 7 dpi (Fig. 1A) indicate that infection initially augmented these reactive species. It must be pointed out that different organs respond in different ways in relation to ROS production, and that a high degree of oxidative stress has been detected in the peripheral blood of chagasic mice.5 However, treatment with DFO promoted an increase in oxidative stress over a longer period of time (i.e. up to 21 dpi), suggesting that this may represent a possible mechanism in the reduction of parasitemia. Nitric oxide (NO) is known to exert microbicidal or microbiostatic effects against many micro-organisms.3 Gradual increases in the levels of nitrate/nitrite in animals of the IT group occurred throughout the post- infection treatment period (Fig. 1D) indicating that the action of DFO must be associated with infection. The increase of nitrate/nitrite in the INT group of animals (data not shown) was expected since T. cruzi infection stimulates the production of tumor necrosis factor-α and interferon-γ, and this culminates in the increased expression of inducible nitric oxide synthase (iNOS) and the subsequent production of NO by macrophages.18 Although details of the mechanism by which iNOS is activated are unclear, infection typically increases NO production by 30%.19 The decrease in hepatic GT concentration in infected animals that had been treated with DFO (Fig. 3A) indicates the ability of the drug to increase the defense of the host against oxidative stress associated infection. Since GT levels in the NIT group were unchanged in comparison with both untreated groups, it is likely that DFO up-regulates GPx only in the presence of T. cruzi infection. Experimental studies have shown that host response to acute infection by T. cruzi involves the up- regulation of the glutathione antioxidant defense system comprising GPx, GSH and oxidized forms of glutathione.1 However, during the progression of Chagas’ disease in mice, glutathione defense becomes non- responsive to chronic oxidative stress and cardiac levels of GPx are reduced; a systemic GPx and SOD down- regulation is also observed in mice and humans under chronic conditions.20,21 It is important to note that trypanosomatids do not possess the selenium-dependent glutathione peroxidase/glutathione reductase system found in other cells.22 In the present study, the levels of SOD in animals of the IT group occurred throughout the post-infection treatment period (Fig. 3B) indicating that the action of DFO must be associated with infection. In this respect, the infection-related effect of DFO is important in increasing the level of the antioxidant enzyme since SOD represents the first line of defense against ROS. It has previously been established that SOD activity in the erythrocytes of patients with mild cardiac impairment was higher than that found in controls, but no differences were detected in SOD activity in different chagasic groups.21 In terms of the glutathione and SOD defense systems, it is clear that DFO exerts an antioxidant action on the hepatocytes of the host that contributes to the protection against oxidative damage caused by Chagas’ disease. Moreover, it would appear that the effects of DFO are apparent at the start of the parasitemia peak, leading to a reduction in the parasitemia curve of T. cruzi in DFO-treated animals as has been shown previously.8,9 It is also possible that DFO causes an increase in the generation of ROS Redox Report 2010 Vol 15 No 4 189