Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice

Abstract

Kim J, Jang HS, Park KM. Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice. Am J Physiol Renal Physiol 298: F158 -F166, 2010. First published October 28, 2009 doi:10.1152/ajprenal.00474.2009.-Ischemic preconditioning by a single event of ischemia and reperfusion (SIRPC) dramatically protects renal function against ischemia and reperfusion (I/R) induced several weeks later. We recently reported that reactive oxygen species (ROS) and oxidative stress were sustained in a kidney that had functionally recovered from I/R injury, thus suggesting an association between SIRPC and ROS and oxidative stress. However, the role of ROS in SIRPC remains to be clearly elucidated. To assess the involvement of ROS in SIRPC, mice were subjected to SIRPC (30 min of bilateral renal ischemia and 8 days of reperfusion) and then exposed to I/R injury. Thirty minutes of bilateral renal ischemia in the non-SIRPC mice resulted in a marked increase in plasma creatinine levels 4 and 24 h after reperfusion, which was not observed in the I/R in the SIRPC mice. SIRPC resulted in increases in the levels of kidney superoxide. Administrations of manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin [MnTMPyP; a cell-permeable superoxide dismutase (SOD) mimetic] and N-acetylcysteine (NAc; a ROS scavenger) to SIRPC mice blocked the SIRPC-induced increase in superoxide levels and removed ϳ48 -64% of the functional protection of the SIRPC kidney. Additionally, these administrations significantly inhibited I/R-induced increases in superoxide formation, hydrogen peroxide production, and lipid peroxidation, along with the inhibition of I/R-induced reductions in the expression and activity of manganese SOD, copper-zinc SOD, and catalase. Furthermore, administrations of MnTMPyP or NAc inhibited the SIRPC-induced increase in inducible nitric oxide synthase expression but did not inhibit the SIRPC-induced increases in heat shock protein-25 expression. In conclusion, the renoprotection afforded by SIRPC was triggered by ROS generated by SIRPC.acute kidney injury; renoprotection; inducible nitric oxygen synthase; heat shock protein ISCHEMIA AND REPERFUSION (I/R) causes acute kidney injury (AKI), which is characterized by high mortality and morbidity, and no effective therapeutic strategy has yet been developed for this condition (3). In addition to direct hypoxic damages induced by reductions in blood flow, I/R injury is associated with a number of factors, including reactive oxygen species (ROS), cytokines, and chemokines, all of which are abundantly generated during I/R (3, 39).ROS are generated under physiological and pathological conditions (9, 38). In physiological conditions, cells produce small amounts of ROS, which could be managed by the scavenging capacity of cells; whereas in pathological conditions they produces excessive ROS, beyond their capacity to scavenge it (9, 29, 38). This excessive ROS generation induces lipid peroxidation, inactivation o...

Endotoxin-induced renal tolerance against ischemia and reperfusion injury is removed by iNOS, but not eNOS, gene-deletion

“…Currently, new evidence is emerging to suggest an association between endotoxin-induced tolerance and increased transcription, novel gene expression, and de novo protein synthesis (16,17). In the heart, NO/NOS has been implicated as a candidate for endotoxin-induced organ tolerance (6), but in the kidney this remains unclear.…”

Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury

“…* p < 0.05 compared to REG 20 week group. buting factor to renal I/R injury [9][10][11]. The AO-fortified diet regimen used in the present study prevented early hyperfiltration in response to I/R injury, but only at 8 weeks of age.…”

“…Exposure to previous insults that increase oxidative stress in the kidney may result in subsequent protection by up-regulated endogenous factors such as superoxide dismutase [10]. In this setting, exogenous antioxidants may only be beneficial during cer-tain time intervals, possibly because of activation of other mechanisms of cellular injury and death, such as inflammation, increased intracellular calcium and activetion of caspases [7] by hypoxemia and acidosis.…”

“…Following the I/R event, oxygen free radicals are released which are very damaging to the kidney. This causes tissue fibrosis, renal dysfunction, and/or rejection [9][10][11]. Further, it has been shown that administering treatments that scavenge oxygen free radicals and have antioxidant properties can ameliorate the damaging results in renal grafts following I/R injury [12][13][14][15].…”

Protective Role of Methionine Sulfoxide Reductase a Against Ischemia/Reperfusion Injury in Mouse Kidney and Its Involvement in the Regulation of Transsulfuration Pathway

“…Kidney oxidative stress induces tissue damage and also accelerates inflammatory responses, including neutrophil accumulation into the kidney tissue, which triggers ROS production, thereby leading to further tissue and cell damage (15,17,36). Inflammatory responses perform an important role in kidney I/R injury.…”