Effect of the Novel Free Radical Scavenger 4′-Hydroxyl-2-Substituted Phenylnitronyl Nitroxide on Oxidative Stress, Mitochondrial Dysfunction and Apoptosis Induced by Cerebral Ischemia–Reperfusion in Rats

Abstract

Mitochondrial dysfunction, which results in the overproduction of oxygen free radicals, is a crucial mechanism underlying cerebral ischemia–reperfusion injury. 4′-Hydroxyl-2-substituted phenylnitronyl nitroxide (HPN), which is an antioxidant and free radical scavenger, can effectively scavenge oxygen free radicals, suggesting its potential as a protective agent against cerebral ischemia–reperfusion injury. In this study, we investigated the effects of HPN on mitochondrial function and apoptosis following cerebral ischemia/reperfusion injury in rats. Healthy adult SD rats were chosen as the experimental subjects, and the rat ischemia/reperfusion injury model was generated using the modified Zea Longa method. The administration of HPN significantly enhanced the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Additionally, HPN effectively preserved the morphology and function of mitochondria, reduced the protein and gene expression of Caspase-3 and Bax, increased the protein and gene expression of Bcl-2, mitigated neuronal apoptosis, improved neurological deficits, and decreased the volume of cerebral infarction. Of interest, the protective effect on brain tissue was more evident with increasing doses of HPN. These findings indicate that HPN can serve as an effective protective agent against cerebral ischemia–reperfusion injury.