As well as the involvement of oxidative stress that occurs during plasmodium infection, determine the influence of renal endothelial modifications to development of malaria-associated AKI and also characterize how HO-1 may participate in both protection and pathogenesis of clinical outcome. In the current study, we provide evidence that describe changes in the pathophysiology of kidney in an experimental model of severe malaria resembling to malaria-associated AKI in P. falciparum malaria. Impairment of renal function during malaria infection has been notified by clinical reports and it is an important life-threatening complication of malaria infection that goes beyond the classical clinical symptoms of plasmodium. The adversities to access of medical services, or delay in diagnosis in their place of origin, are implicated in the severity of disease. The onset of kidney injury in BALB/c infected mice come out from day 4 after infection and the incidence of renal failure was confirm through manifestations such as PD325901 increased of plasma creatinine and blood urea nitrogen levels, as well as a decrease of total erythrocyte PpIX concentration in infected mice. This data reinforces the idea that the decrease of fluorescence emission of erythrocyte protoporphyrin IX, an intermediate product in the biosynthesis of heme, may be set up as a marker of several diseases as renal injury. The pathophysiology of severe malaria are usually associated with a polyclonal activation of the immune system and comprehends a complex network with production of reactive oxygen and nitrogen species, such as IFN-c, TNF-a, IL-6, IL-1 and IL-8, as well by nuclear translocation of NF-kB. In agreement with this notion, our study demonstrated that malaria infection markedly increase IFN-c mRNA expression, as well protein expression of IL-1b, IL-6 and TNF-a in renal tissue of P. berghei ANKA infected mice, consistent with a previous study. The upregulation of protein expression of IKK in renal tissue support the idea that NF-kB pathway is required for this proinflammatory profile, as well as iNOS gene expression during malaria infection. Malaria-associated AKI is proposed to be a consequence of parasite adhesion as well as exacerbated immune response against products of oxidative stress released during infection. The destruction of erythrocytes during blood stage of infection accumulates high levels of toxic free heme in circulation that, in turn, has the ability to induce oxidative stress from production of hydroxyl radicals via the Fenton/Haber-Weiss reaction. Moreover, heme-derived oxidative stress is considered to be a main factor in the iron-induced lipid peroxidation resulting in the formation of oxidized LDL. The results presented here strongly suggest that plasma oxidizability in BALB/c infected mice may results to free radicals generated from increased plasma levels of heme. Therefore, our data might add new insights to previous findings demonstrating the lipid peroxidation mediated by heme-induced oxidative stress during infection by P. berghei ANKA. Plasma oxidation assay measured by dienes absorption at 234 nm provide results as observed at ox-LDL plasma levels and it is a well-known index to determine oxidizability of plasma lipoproteins. In addition, the mRNA expression of lectinlike oxidized LDL receptor was also marked increased in renal tissue of infected mice. LOX-1 could be rapidly expressed in endothelial cells, macrophages, vascular smooth muscle cells and glomerular mesangial cells induced by products of oxidative stress, as well as pro-inflammatory cytokines.