Oxidative and nitrosative stress in acute renal ischemia

Abstract

First Published July 12, 2001; 10.1152/ajprenal.0071.2001.—Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable of causing lipid peroxidation and DNA damage. This study was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in ischemic acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine modification confirmed both by Western and immunohistochemical analyses. Three groups of animals were randomly treated with an inhibitor of inducible nitric oxide synthase (NOS),l- N 6-(1-iminoethyl)lysine (l-Nil), cell-permeable lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in amelioration of renal dysfunction, as well as reduced nitrotyrosine formation, lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather than superoxide anion is responsible for lipid peroxidation and DNA damage. Therefore, in a separate series of experiments, a scavenger of peroxynitrite, ebselen, was administered before the reperfusion period. This treatment resulted in a comparable degree of amelioration of iARF. In conclusion, the present study provides the first attempt to elucidate the role of peroxynitrite in initiation of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The results demonstrate that l-Nil , lecithinized SOD, and ebselen treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

Prevention and Treatment of Acute Renal Failure in Sepsis

“…The effect was due to an attenuation of tubular injury, suggesting cytotoxic effects of NO produced by iNOS during renal ischemia. Similarly, the selective iNOS inhibitor L-N 6 -(1-iminoethyl)lysine (L-NIL) conferred renoprotective effects during ischemia (62). Selective iNOS inhibition with S-methyl-isothiourea prevented hypotension through systemic vasoconstriction and maintained cardiac output and reduced the signs of renal dysfunction in rats challenged with LPS (63).…”

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

“…[4] Although all molecules are susceptible to ROS injury, lipids are targeted most frequently. Several studies have demonstrated that ROS can produce cellular injury by attacking membranes through peroxidation of polyunsaturated fatty acids that can alter both membrane structure and function of mitochondrial, lysosomal, and cell membrane via lipid peroxidation [1,5,6] . Malondialdehyde (MDA) is an end product of lipid peroxidation and widely accepted as a marker of ROS-mediated lipid peroxidation in the cell.…”

Cutting Edge: MHC Class II-Restricted Peptides Containing the Inflammation-Associated Marker 3-Nitrotyrosine Evade Central Tolerance and Elicit a Robust Cell-Mediated Immune Response

“…3 Accumulation of protein-associated nitrotyrosine has been documented in inflammatory conditions of diverse origin such as atherosclerosis (1), respiratory disease (2), transplant rejection (3), multiple sclerosis (4), Alzheimer's disease (5), celiac disease (6), arthritis (7)(8)(9), ischemia-reperfusion injury (10), autoimmune diabetes (11), autoimmune uveitis (12), and infectious diseases (13). Although the precise molecular mechanism(s) responsible for in vivo formation of nitrotyrosine is still not firmly established, peroxynitrite and other reactive nitrogen species generated during periods of inflammation are thought to be primary intermediates (14,15).…”