Ischemia–reperfusion injury pathophysiology, part I

Abstract

Objective: To review the current scientific literature on ischemia–reperfusion (IR) injury in both human and veterinary medicine. To describe the normal antioxidant defense mechanisms, the pathophysiology of IR injury, and the role of neutrophils in IR injury. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: IR injury is a complex pathophysiological process involving numerous pathways and body systems. Normal antioxidant defense mechanisms function to limit oxidative injury during times of health. Ischemia is the period that occurs before oxygenated blood is re‐introduced and the severity of injury has been shown to correlate with the magnitude and length of ischemia in dogs. During ischemia, there is a buildup of substances (i.e., xanthine oxidase, hypoxanthine, etc.) that, upon re‐introduction of oxygen, form reactive oxygen species (ROS). ROS, produced in large part upon reperfusion, can cause extensive damage to DNA, proteins, carbohydrates, and lipids. Although mammalian systems are endowed with abundant antioxidant defenses, the generation of large amounts of ROS can overwhelm these mechanisms leading to cell dysfunction and death. Neutrophils play a critical role in IR injury and may mediate the majority of mucosal and microvascular injury that occurs by releasing ROS and proteolytic enzymes. Although experimental studies have been carried out on cats, dogs, and horses there are few clinical studies on companion animals. Conclusions: The pathophysiology of IR injury is complex and involves damage by ROS to all biological membranes. Neutrophils play a major role in IR injury and initiate and propogate much of the damage. This article is intended as a review of the pathophysiology of IR injury.

The Protective Effects of Ascorbic Acid against Renal Ischemia-Reperfusion Injury in Male Rats

“…[25] Thus, ROS are believed to play a central role in I/R injury in addition to several other diseases, including neoplasia, atherosclerosis, and neurodegenerative diseases. [8] ROS are capable of reacting with proteins, lipids, and nucleic acids leading to the lipid peroxidation of biological membranes, which in turn impacts upon enzymatic processes such as ion pump activity [15,26] . Previous experiments show that various exogenous antioxidant agents such as allopurinol, melatonin, tocopherol, leflunomide, and some flavonoids have the potential to reduce I/R induced-renal injury and help the improvement of kidney function.…”

“…antioxidant systems. [8] Like other cells, kidney cells have these antioxidant defenses to cope with potential oxidative damages. Unfortunately, the level of these endogenous enzymes and antioxidant compounds become insufficient during I/R events due to abundant ROS formation.…”

Inhibiting inducible nitric oxide synthase with rutin reduces renal ischemia/reperfusion injury

“…2,39,[41][42][43] Reactive oxygen and nitrogen species are believed to play a central role in I/R injury in addition to several other factors, such as neutrophils, platelets, the coagulation system and the xanthine-oxidoreductase enzyme system. Our previous report demonstrated that renal I/R worsened the renal dysfunction, oxidative stress and histopathologic features in rats.…”

“…1 Many scientists report that renal I/R injury is a common cause of renal cell death, acute renal failure and, in the case of transplantation, delayed graft function or graft rejection. [2][3][4] Many mediators are involved in the pathophysiology of I/R injury, including reactive oxygen species (ROS), reactive nitrogen species (RNS), purine metabolites, neutrophil accumulation, vasoactive substance (endothelin, angiotensin II) and subsequent release of lytic enzymes. [5][6][7] Nitric oxide (NO), a soluble, free radical gas, has an astounding range of biological roles, including modulation of vascular tone and inflammation.…”

Choque circulatório em equinos

“…Embora seja necessária para a sobrevivência celular, a reperfusão cria mais injúria do que a isquemia em decorrência da grave disfunção endotelial que promove. A disfunção endotelial resulta da maciça formação de radicais livres, diminuição da liberação de óxido nítrico e acentuada liberação de endotelina, criando um estado de intensa vasoconstrição e consequente diminuição da perfusão periférica (MCMICHAEL;MOORE, 2004).…”