Renal ischemia/reperfusion injury in rats is attenuated by a synthetic glycine derivative.

Abstract

Renal ischemia/reperfusion is a common cause of acute renal failure. Glycine is an effective anti-inflammatory, cytoprotective agent and is reported to have a beneficial effect against ischemia/reperfusion injury in various organs. Previous research notes that free radicals and inflammatory leukocytes both play important roles in the pathogenesis of renal ischemia/reperfusion injury. To develop new therapeutic agents against renal ischemia/reperfusion injury, we sought to link an antioxidant moiety (nitronyl nitroxide) to glycine in the hope that the resulting glycine-nitronyl nitroxide conjugate (GNN) would provide a synergetic protection against renal ischemia/reperfusion injury. In this manuscript, we report the synthesis and biological evaluation of the GNN conjugate. The biological activity of the GNN conjugate was evaluated in an in vivo rat model of renal ischemia/reperfusion induced injury and oxidative change. Since the GNN conjugate markedly reduced elevated levels of tissue lipid peroxidation and attenuated renal dysfunction in rats subjected to renal ischemia/reperfusion, it might be possible to develop the GNN conjugate into a potential therapeutic agent against renal ischemia/reperfusion injury.

• Authors: Wei Bi, Fengan Wang, Yue Bi, Tianyang Wang, Ping Xue, Yanrong Zhang, Xiang Gao, Sanguang Liu, Zhibo Wang, Meng Li, Michèle Baudy-Floc'h, Sara C Robinson, Nathaniel Ngerebara, Lanrong Bi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 616 Issue 1-3 Pg. 256-64 (Aug 15 2009) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19555683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Inflammatory Agents
• Free Radical Scavengers
• Nitrogen Oxides
• Malondialdehyde
• Peroxidase
• Glutathione
• nitroxyl
• Acetylcholine
• Glycine

Topics

• Acetylcholine (pharmacology)
• Animals
• Anti-Inflammatory Agents (chemistry)
• Blood Urea Nitrogen
• Free Radical Scavengers (chemical synthesis, chemistry, pharmacology)
• Glutathione (metabolism)
• Glycine (analogs & derivatives, chemical synthesis, pharmacology, therapeutic use)
• In Vitro Techniques
• Kidney (blood supply, drug effects, metabolism)
• Male
• Malondialdehyde (metabolism)
• Nitrogen Oxides (chemistry)
• Oxidative Stress (drug effects)
• PC12 Cells
• Peroxidase (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Vasodilation (drug effects)