Similarities between ozone oxidative preconditioning and ischemic preconditioning in renal ischemia/reperfusion injury

Arch Med Res. 2008 Feb;39(2):169-78. doi: 10.1016/j.arcmed.2007.09.005. Epub 2007 Nov 28.


Background: Many studies indicate that the production of reactive oxygen species (ROS) after renal ischemia/reperfusion (I/R) may initiate the cascade of cellular injury. It has been demonstrated that ozone oxidative preconditioning (OzoneOP) may prevent the damage induced by ROS and attenuate renal I/R injury. On the basis of those results, we postulated that OzoneOP was similar to the ischemic preconditioning (IP). The aim of our present work was to assess whether the combination of OzoneOP and IP provided synergistic protection.

Methods: Seven groups of rats were classified as follows: 1) sham-operated control; 2) I/R; 3) OzoneOP+I/R; 4) IP+I/R; 5) OzoneOP+IP+I/R; 6) O2+I/R; 7) sham-operated control+OzoneOP. Rats were sacrificed at 24 h after I/R injury. Serum and tissue were taken to determine urea nitrogen (BUN), creatinine (Cr), nitric oxide (NO), histological examination, and NO synthase (endothelial, eNOS and inducible, iNOS) expression. Malondialdehyde (MDA) content, glutathione (GSH) content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity were determined in renal tissue.

Results: Renal dysfunction, histological damage, and renal oxidative stress were significantly improved by OzoneOP or IP alone. OzoneOP+IP could not further relieve severe renal damage. Either IP or OzoneOP treatment alone increased NO release and NO synthase (endothelial, eNOS and inducible, iNOS) expression. The combination of OzoneOP and IP could not further enhance NO levels and NOS expression.

Conclusions: These findings indicate that both of the preconditioning settings shared similar mechanisms of protection in the parameters measured. However, OzoneOP combined with IP had no synergistic effect. IP and OzoneOP appeared to share a common mediator: NO. These findings suggested the potential role of OzoneOP against renal failure during surgery or transplantation.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Ischemic Preconditioning*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Male
  • Nitric Oxide / metabolism
  • Oxidants, Photochemical / pharmacology*
  • Ozone / pharmacology*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*


  • Biomarkers
  • Oxidants, Photochemical
  • Nitric Oxide
  • Ozone