Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion injury in the rat by an antioxidant action via inhibition of NADPH oxidase and iNOS expression.

Abstract

AIMS:

This study was conducted to investigate the protective effects of CXC195, a tetramethylpyrazine analogue, in acute focal cerebral ischemia/reperfusion (I/R) injury in rats and to elucidate the potential mechanism.

METHODS:

Middle cerebral artery occlusion for 2 h followed by reperfusion for 24 h was conducted in male Wistar rats and different doses of tetramethylpyrazine and CXC195 were intraperitoneally injected at 30 min after reperfusion.

RESULTS:

Our results demonstrated that CXC195 at the dosage of 3 and 10 mg/kg significantly reduced the neurological deficit score and the infarct volume compared to the vehicle-treated group. In addition, CXC195 exhibited a protective effect against hippocampus neuronal cell death and significantly restored the brain ATP content. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidative capability (T-AOC), as well as production of malondialdehyde (MDA) and reactive oxygen species (ROS) were assayed in ipsilateral hemisphere homogenates to evaluate the redox status after I/R injury. Treatment with CXC195 significantly attenuated the decrease of SOD, GPx and T-AOC activities and inhibited the elevation of MDA content and ROS generation. Furthermore, CXC195 prevented the upregulation of the NADPH oxidase (NOX) 2 and NOX4, and reduced inducible nitric oxide synthase (iNOS) induction and production of nitric oxide induced by I/R.

CONCLUSION:

These results suggest that CXC195 has a neuroprotective effect in transient focal ischemia, which is most likely due to its antioxidant activity by inhibiting NOX and iNOS expression.

• Authors: Huiqing Liu, Xinbing Wei, Lin Chen, Xiaoqian Liu, Senpeng Li, Xinyong Liu, Xiumei Zhang
• Journal: Pharmacology (Pharmacology) Vol. 92 Issue 3-4 Pg. 198-206 ( 2013) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 24107713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 S. Karger AG, Basel.

Chemical References

• Antioxidants
• CXC 195
• Membrane Glycoproteins
• Neuroprotective Agents
• Piperazines
• Pyrazines
• Nitric Oxide
• Adenosine Triphosphate
• Glutathione Peroxidase
• Nitric Oxide Synthase Type II
• Nos2 protein, rat
• Superoxide Dismutase
• Cybb protein, rat
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, rat

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antioxidants (pharmacology, therapeutic use)
• Brain (drug effects, metabolism, pathology)
• Brain Ischemia (drug therapy, metabolism)
• Glutathione Peroxidase (metabolism)
• Male
• Membrane Glycoproteins (metabolism)
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Piperazines (pharmacology, therapeutic use)
• Pyrazines (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Reperfusion Injury (drug therapy, metabolism)
• Superoxide Dismutase (metabolism)