Reactive Oxygen and Nitrogen Species in the Renal Ischemia/Reperfusion Injury

Abstract

Renal ischemia is the most common cause of acute kidney injury (AKI) still associated with high mortality rates of about 50% in the intensive care unit. Postischemic AKI is characterized by decreased glomerular filtration rate and high renal vascular resistance with endothelial activation and dysfunction, a process of critical importance that is followed by a reduction in microvascular blood flow mainly affecting the renal outer medulla. The pathophysiology of postischemic AKI remains incompletely understood, although it seems to be a phenomenon of altered renal hemodynamics, linked critically to the production of high amounts of nitric oxide and free radicals. On the other hand, and depending on the severity of renal ischemia, tubular epithelial cells undergo a varying degree of necrosis or apoptosis with tubular obstruction followed by both, anatomical and functional recovery. The way in which vascular and tubular epithelium recover determines the final status of the renal function, ranging from full recovery to chronic renal failure and ultimately to end-stage renal disease. In this review we will revise the mechanisms responsible for these pathophysiologic alterations, including the role of heme oxygenase system and sex differences in the susceptibility to ischemic acute renal failure, and we will also review the pre- and postconditioning phenomena, in which brief episodes of ischemia before (pre-conditioning) or after (post-conditioning) the prolonged ischemia have a protective effect on AKI after reperfusion. Interestingly, these protective responses can be elicited by ischemizing distant tissues (remote conditioning). A better understanding of these mechanisms may help to improve the clinical outcome of those patients.

Ischemia-Reperfusion Injury in Stroke

“…Both processes have been linked to further stimulation of the inflammatory system to include the release of nucleotides acting as signals to promote phagocytosis in the apoptotic tissue bed, leading to more extensive reperfusion injury [19,22]. Additional injury to reperfused tissue has been extensively shown to be mediated by reactive radical oxide species in the brain as well as in other tissues [23,24,25,26,27,28]. The mechanism of tissue damage occurs at both the cellular and molecular levels.…”

The Role of Hypoxia-Inducible Factors in Organ Donation and Transplantation: The Current Perspective and Future Opportunities

“…EPO and HO-1 up-regulators, for example, have undergone extensive evaluation and remain to be established as to whether they are of clinical value (16). This review focuses on HIF as an upstream target in kidney, liver, cardiac and lung transplantation.…”

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

“…2 Ischemic renal injury leads to a rise in antibody production, which may be harmful to renal allografts, possibly explaining a mechanism underlying the link between delayed graft function and long-term allograft failure. 3 Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a and interleukin (IL)-1b, are increased after ischemia/ reperfusion (IR) in some model systems.…”