Effect of combination therapy with pramipexole and n-acetylcysteine on global cerebral ischemic reperfusion injury in rats

OBJECTIVE(S): The study was intended to investigate the combined influence of two neuroprotective agents pramipexole and n-acetylcysteine on global cerebral ischemic reperfusion injury (GCIRI) model in rats. MATERIALS AND METHODS: GCIRI was induced by bilateral common carotid artery ligation (BCCA) in rats. Animals were divided into six groups. Groups I, II, and III received saline intraperitoneally (IP) (5 ml/kg/day, 0.9 % saline). The remaining groups IV, V, and VI were treated with n-acetylcysteine (NAC-150 mg/kg/day, IP), pramipexole (PPX-0.23 mg/kg/day, IP) alone and in combination, respectively. BCCA was done in all groups except in groups I (control) and II (sham control) of animals. The treatment was given for one week before the surgery and continued for two days after surgery. Subsequently, behavioral performances, biochemical estimations, proinflammatory cytokines, and histopathological evaluations were done. RESULTS: NAC, PPX, and combination treatment groups showed significant ameliorative effects on behavioral, biochemical, proinflammatory cytokines, and histopathological studies as compared with the BCCA group. Whereas, the combination group showed a significant difference in ameliorating the pathological changes of biochemical parameters and histopathological changes in comparison with the PPX alone treated group but not with the NAC alone group. CONCLUSION: The study concluded that in the combination treatment group the histopathological parameter improved and the oxidative stress parameters were mitigated significantly compared with the PPX alone treatment group but not with the NAC alone treatment group.