Protective effect of nitronyl nitroxide-amino acid conjugates on liver ischemia-reperfusion induced injury in rats

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1788-94. doi: 10.1016/j.bmcl.2008.02.030. Epub 2008 Feb 16.

Abstract

Stable nitroxides are potential antioxidant drugs. In this study, we have linked nitroxide to natural amino acids with the aim to improve therapeutic activity. The radical scavenging activities of two nitronyl nitroxide-amino acid conjugates (NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. In addition, the protective effect of NNR was demonstrated in an in vivo rat model of hepatic ischemia-reperfusion (I/R) induced injury and oxidative change. Because NNR reduced hepatic I/R injury by minimizing oxidative stress, it might be possible to develop it into a possible therapeutic agent for hepatic I/R injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Alanine Transaminase / metabolism
  • Amino Acids / chemical synthesis
  • Amino Acids / chemistry*
  • Amino Acids / pharmacology
  • Animals
  • Antioxidants / therapeutic use
  • Aorta, Thoracic / drug effects
  • Aspartate Aminotransferases / metabolism
  • Cell Survival / drug effects
  • Electron Spin Resonance Spectroscopy
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / pharmacology
  • Free Radicals / chemistry
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Malondialdehyde / metabolism
  • Molecular Structure
  • Nitrogen Oxides / chemistry*
  • Oxidative Stress / drug effects*
  • PC12 Cells
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Vasodilation / drug effects

Substances

  • Amino Acids
  • Antioxidants
  • Free Radical Scavengers
  • Free Radicals
  • Nitrogen Oxides
  • Reactive Oxygen Species
  • Malondialdehyde
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Acetylcholine