Effect of a novel inducible nitric oxide synthase inhibitor, FR260330, in prevention of renal ischemia/reperfusion injury in vervet monkeys.

Abstract

Cytotoxic nitric oxide (NO) is produced during ischemia/reperfusion (I/R) injury by the expression of inducible NO synthase (iNOS). Therefore, continuous iNOS inhibition might prevent early graft dysfunction. FR260330, a potent and selective inhibitor of iNOS activity, impedes the dimmerization of iNOS monomer. In this study, the effect of FR260330 in the prevention of renal I/R injury was evaluated in the model of one kidney ischemia in Vervet monkeys. A total of 18 male Vervet monkeys were randomly assigned to two equal groups (n=9). Transient (60 min) left renal ischemia was produced by simultaneous contralateral nephrectomy in treated (FR260330 20 mg/kg/day) and placebo control groups. Renal function and other biochemical parameters as well as FR260330 concentrations were studies until day 15 after I/R injury. All monkeys survived after 60 min I/R injury until sacrifice on day 15. Serum creatinine in the untreated controls increased significantly in comparison to the FR260330-treated group on days 2, 3, 4, and 7 (P<0.05). Plasma FR260330 concentration after oral administration showed that C(max) was 3.251+/-2.526 microg/ml, and T(max) was 4 hr. This study thus finds that FR260330, as a selective iNOS inhibitor, effectively prevents renal I/R injury in Vervet monkeys.

• Authors: Shijie Qi, Dasheng Xu, Anlun Ma, Xiaochun Zhang, Noboru Chida, Yuji Sudo, Kouichi Tamura, Pierre Daloze, Huifang Chen
• Journal: Transplantation (Transplantation) Vol. 81 Issue 4 Pg. 627-31 (Feb 27 2006) ISSN: 0041-1337 [Print] United States
• PMID: 16495814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• FR260330
• Piperidines
• Nitric Oxide Synthase Type II

Topics

• Animals
• Chlorocebus aethiops
• Enzyme Inhibitors (pharmacology)
• Kidney (blood supply)
• Male
• Models, Animal
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Piperidines (pharmacology)
• Reperfusion Injury (prevention & control)