Renal ischaemia-reperfusion injury

Abstract

Ischaemia-reperfusion injury is a complex interrelated sequence of events that classically involves the vascular endothelium and activated leucocytes. During the ischaemic phase the endothelium is primed both to produce free radicals and to secrete chemoattractants. The resultant neutrophil sequestration serves to amplify the injury, but damage is not confined to the postischaemic area and more generalized effects typically follow. The situation in the kidney is complex for, while ischaemia primes the tissue for reperfusion damage, it also causes early and irreversible tubular injury. Furthermore, it appears that relatively less importance should be attached to the involvement of neutrophils than at other sites, and relatively more to a local postischaemic imbalance in the levels of nitric oxide and endothelin. Despite a greater understanding of the pathogenesis of ischaemia-reperfusion injury, effective treatment remains elusive and research is hampered by apparent species and organ-specific differences.

Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation

“…3,4 Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes, and their destruction can lead to the production of toxic reactive aldehydic metabolites and cell death. [5][6][7][8] A range of drugs and methods have been tested with the intention to block the pathways of cell injury at different levels and to thereby enhance viability of the kidney challenged by ischemia/ reperfusion stress with variable results, such as: heat shock (interferes with the L-arginine-nitric oxide pathway), 9 antioxidants, 10,11 dipyridamole (increases endogenous adenosine), 12,13 nicotine (inhibit cholinergic antiinflammatory pathway), 14 calcium channel blockers or antagonists, [15][16][17][18] chlorpromazine, 19,20 etc. Chorpromazine (CPZ) is a membrane stabilizer and seems to be able to preserve mitochondria integrity and to reduce phospholipids degradation of microsomal membranes of liver cell provoked by ischemia/reperfusion.…”

“…Chorpromazine (CPZ) is a membrane stabilizer and seems to be able to preserve mitochondria integrity and to reduce phospholipids degradation of microsomal membranes of liver cell provoked by ischemia/reperfusion. 20,21 The aim of our study was to explore the effect of chlorpromazine on renal function and membrane lipid peroxidation in a rat model of renal ischemia/reperfusion.…”

Betulinic acid protects against ischemia/reperfusion‐induced renal damage and inhibits leukocyte apoptosis

“…Although many have been evaluated clinically with a view to reducing renal I/R injury and improving renal function, none has been able to reduce mortality signifi cantly. I/R induced organ damage is multifactorial and interdependent, involving hypoxia, infl ammatory responses and free radical damage (Weight et al, 1996;Chatterjee, 2007;Boros and Bromberg, 2006). Thus, agents with antioxidant and antiinfl ammatory effects are thought to be useful in the clinical setting of I/R damage.…”

“…superoxide radicals, hydroxyl radicals, hydrogen peroxide) and lipid mediators (e.g. platelet activating factor and leukotriene B4) (Weight et al, 1996;Werns and Lucchesi, 1990). Thus the mechanisms underlying I/R damage to the kidneys are most likely multifactorial, and interdependent involving hypoxia, infl ammatory responses and free radical damage.…”

Gene therapy in transplantation

“…10,11 Among the mechanisms that can contribute to ischemia/reperfusion injury (IRI) one can include neutrophil infiltration, consequent to the effects of proinflammatory cytokines released at the site of injury. [12][13][14] Kidneys that were mildly ischemic and then perfused with primed neutrophils underwent acute renal failure. 15 In general, neutrophil infiltration begins under the direction of chemotactic factors such as IL-8 and other chemokines.…”