The maintenance of proinflammatory state by ox-LDL plays an important role to modulate the up-regulation of ICAM-1, that induces adverse outcomes on renal microvascular permeability through leukocyte adherence, sequestration and adhesion of infected red blood cells to renal endothelial cells. Addionally, ox-LDL also increases iNOS expression in renal tissue, during an intestinal ischemia/reperfusion injury. iRBC sequestration at the microvascular site is an important feature of severe malaria. It has been shown that P. falciparum iRBC cytoadherence occurs via interactions of parasite surface antigen to endothelial receptor including ICAM-1 and CD36. In this work we found an increase of ICAM-1 expression on renal tissue from P. berghei infected mice at day 7 post infection. Interestingly, ex vivo adhesion assays using sections from renal tissue from infected mice at this time-point show increased iRBC adhesion. Taken together, these results suggest that P. berghei interaction with the renal tissue can occur via ICAM-1. Therefore, we assume that exposition of endothelial cells to products of oxidative stress and parasite load plays a crucial role to endothelial activation and microvascular dysfunction in infected kidneys, concomitant with a markedly upregulation of ICAM-1 in renal tissue. The cytoadherence of infected erythrocytes as well recruitment of monocytes, neutrophils and polymorphonuclear leukocytes, during pathogenesis of malaria-associated AKI could potentially contribute to renal hypoxia. In addition, an up-regulation of hypoxia inducible factor-1a mRNA and decrease of angiogenic factors protein expression in renal tissue can further induce morphological Navitoclax modifications. Changes in vascular permeability observed were quite expected, since microvascular dysfunction has been described before in the pathogenesis of ischemic-induced AKI. Recruitment of inflammatory cells during pathogenesis of malaria-associated AKI is in line with previous observations about involvement of infiltrating cells to increase vascular permeability. This proinflammatory state also contributes to increase the occurrence of apoptotic events. Usually, the exposition of host endothelial cells to free heme triggers an up-regulation of HO-1, an inducible enzyme that catalyzes the degradation of toxic heme. In response to oxidative stress, HO-1 limits inflammation-associated tissue damage through the generation of product of catabolism of toxic heme as molecules of CO, bilirubin and ferritin. Previous reports from our group have demonstrated a cytoprotective role of HO-1 in models of renal injury and ischemia and reperfusion events. Moreover, HO-1 also prevents the development of experimental cerebral malaria, modulates the proinflammatory response during liver stage of P. berghei ANKA infection, as well as prevents hepatic injury in a noncerebral severe malaria infection. Despite of above observations, we have found an impairment of mRNA expression of HO-1 in renal tissue, even as a decreased plasma level of indirect bilirubin. Antiinflammatory and cytoprotective molecules were also downregulated. Taken together, our data suggest that both, proinflammatory molecules and products of oxidative stress have a central role to development of the pathogenesis of malaria-associated AKI. Our results also suggest that the loss of integrity of the renal vascular endothelium during infection are multifactorial in origin and may be related to increased toxic heme levels, reactive oxygen and nitrogen species, as well high levels of proinflammatory molecules.