https://www.amjmed.com/article/S0002-9343(00)00612-4/pdf

Reactive oxygen species and acute renal failure

The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.

/pdf/mitochondria-targeted-peptide-accelerates-atp-recovery-and-2598qo43bv.pdf

Mitochondria-Targeted Peptide Accelerates ATP Recovery and Reduces Ischemic Kidney Injury

Reactive oxygen species have been implicated in the pathophysiology of renal ischemia reperfusion injury. Antioxidants including polyphenolics have been found to protect renal cells from the cellular injury induced by ischemia and reperfusion. Resveratrol, a stilbene polyphenol found in grapes and red wine, has recently been found to protect isolated rat heart from ischemia reperfusion injury. This study was sought to determine if resveratrol could also protect renal cells from ischemic injury. Male Wistar rats were treated with control, resveratrol (0.23 microg/kg), vehicle used to solubilize resveratrol, and resveratrol plus L-NAME (15 mg/kg body wt), a nitric oxide blocker. Our results demonstrated that resveratrol administration reduced the mortality of ischemic rats from 50% to 10% and renal damage was reduced as indicated by histologic examination and serum creatinine level. The short-term administration of resveratrol also inhibited renal lipid peroxidation induced by ischemia and reperfusion both in cortex and in medulla. Electron paramagnetic resonance detected an increased formation of nitric oxide in the resveratrol-treated kidney that was reduced to the baseline value after treating the rats with L-NAME in addition to resveratrol. The results suggest that resveratrol reduced the renal ischemia reperfusion injury through a nitric oxide-dependent mechanism.

Resveratrol, a polyphenol found in wine, reduces ischemia reperfusion injury in rat kidneys.

Oxidative stress and reactive nitrogen species generation during renal ischemia.

Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: Attenuation by dehydroepiandrosterone

https://www.kidney-international.org/article/S0085-2538(15)30702-X/pdf

Protection from renal ischemia-reperfusion injury by the 2-methylaminochroman U83836E

https://air.unimi.it/bitstream/2434/182487/2/34-Influence%20of%20the%2021-aminosteroid.pdf

Paola Rinaldi

Papers

Protection from renal ischemia-reperfusion injury by the 2-methylaminochroman U83836E

Influence of the 21-aminosteroid U74389F on ischemia-reperfusion injury in the rat.