Molecular Dissection of Renal Ischemia-Reperfusion: Oxidative Stress and Cellular Events

Abstract

Ischemic reperfusion kidney injury (IRKI) is a complex pathophysiological event, which is the most common cause of the acute kidney injury. The key characteristic of IRKI is a reduction in glomerular filtration rate, which implies an underlying impairment in hemodynamic regulation. In recent decades, convincing evidence illuminated the molecular and pathological events in the acute kidney injury, revealing the role of ischemia/reperfusion, oxidative stress, apoptosis, inflammation, fibrosis and changes in gene expression which activate different signaling pathways. The cascade of inflammation events is a key mediator of IRKI, which includes the inflammation process, complement activation and mobilization of innate immunity. Oxidative stress represents the increased presence of various free radicals that cannot be buffered by the antioxidant capacity which comprises of enzymatic and non-enzymatic components. Renal tissue injury during ischemia/reperfusion comes as a result of membrane lipids peroxidation, oxidative damage of proteins and DNA and results in apoptosis and necrosis. It is evident from many studies that augmentation of the antioxidant defense mechanisms has a protective role on kidney tissue. In recent years, the importance of heat-shock proteins and MicroRNAs in the pathogenesis of IRKI has been revealed and there are promising indications that in future they could serve as diagnostic biomarkers or therapeutic targets. Striking changes in global gene expression were shown, providing a great potential for fundamental understanding and clinical management of IRKI. The clinical outcome among patients with kidney transplantation will have the furthermost advance from the better understanding of the underlying molecular pathology of IRKI.

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p

“…Recently, miRNAs have been involved in the cell response to I/R in kidney30. Related to this, here we demonstrated that in vivo HIF-1α interference leads to a lower expression of miR-127-3p and, consequently, increased expression of its target gene Bcl6, a transcriptional repressor involved in apoptosis31 and survival regulation32.…”

Oxidative Stress and Acute Kidney Injury in Critical Illness: Pathophysiologic Mechanisms—Biomarkers—Interventions, and Future Perspectives

“…In oxygen deprivation, anaerobic glycolysis is enhanced, lactic acid is accumulated, mitochondrial dysfunction is enhanced, and production of ROS and superoxide is upregulated [53]. The injury expands after reperfusion that is characterized by inflammatory response with leukocyte and complements activation that progresses to an oxidant environment that cannot be counterbalanced by antioxidant mechanisms [54] and uneventfully leads to excessive cell death [53]. …”

Protective Effect of p-Coumaric Acid as Free Oxygen Radical Scavenger in Experimental Renal Ischemia-Reperfusion Model

“…1 The damage is further complicated by the release of oxygen-derived free radicals into the tissue, although reperfusion is necessary for ischemic tissue survival. 2 Renal ischemia-reperfusion (R-IR) injury may be resulted in due to renal transplantation, shock, sepsis and surgical procedures despite great clinical efforts. 3 IR injury is the primary cause of high mortality in acute renal insuffi ciency, the R-IR model in fi ghting against this injury is used in experimental studies widely.…”