Oxidative and nitrosative stress in acute renal ischemia

E. Noiri, A. Nakao, K. Uchida, Hirokazu Tsukahara, M. Ohno, T. Fujita, S. Brodsky, M. S. Goligorsky

Research output: Contribution to journalArticle

287 Citations (Scopus)

Abstract

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-N6-(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.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume281
Issue number5 50-5
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Lipid Peroxidation
DNA Damage
Oxidative Stress
Ischemia
Kidney
Acute Kidney Injury
Nitric Oxide Synthase Type II
Renal Artery
Reperfusion Injury
Constriction
Superoxides
Reperfusion
Reactive Oxygen Species
Nitric Oxide

Keywords

  • 4-hydroxy-2-nonenal
  • 8-hydroxy-2′-deoxyguanosine
  • Ebselen
  • L-N- (1-iminoethyl)lysine
  • Lecithinized superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Noiri, E., Nakao, A., Uchida, K., Tsukahara, H., Ohno, M., Fujita, T., ... Goligorsky, M. S. (2001). Oxidative and nitrosative stress in acute renal ischemia. American Journal of Physiology - Renal Physiology, 281(5 50-5).

Oxidative and nitrosative stress in acute renal ischemia. / Noiri, E.; Nakao, A.; Uchida, K.; Tsukahara, Hirokazu; Ohno, M.; Fujita, T.; Brodsky, S.; Goligorsky, M. S.

In: American Journal of Physiology - Renal Physiology, Vol. 281, No. 5 50-5, 2001.

Research output: Contribution to journalArticle

Noiri, E, Nakao, A, Uchida, K, Tsukahara, H, Ohno, M, Fujita, T, Brodsky, S & Goligorsky, MS 2001, 'Oxidative and nitrosative stress in acute renal ischemia', American Journal of Physiology - Renal Physiology, vol. 281, no. 5 50-5.
Noiri, E. ; Nakao, A. ; Uchida, K. ; Tsukahara, Hirokazu ; Ohno, M. ; Fujita, T. ; Brodsky, S. ; Goligorsky, M. S. / Oxidative and nitrosative stress in acute renal ischemia. In: American Journal of Physiology - Renal Physiology. 2001 ; Vol. 281, No. 5 50-5.
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