Protective Impact of Combined Perindopril and Coenzyme Q10 Treatment Against Cerebral Ischemia/Reperfusion Injury in Male Rats

Abstract

Background: Cerebral ischemia is reason of death and disability worldwide with 11.6\% of all death and 5.7\% of the total disability. Thrombosis and embolism of a major cerebral artery, mainly the middle cerebral artery, account for over 70\% of stroke cases. The other major type of stroke is cerebral hemorrhage either intracerebral or subarachnoid hemorrhage. The oxygen requirements of the nervous tissue are excessively high bringing the brain highly susceptible to ischemia. The subsequent reperfusion after brain ischemia can precipitate more brain injury. Objectives: Assess the neuroprotective effects of perindopril and coenzyme Q10 in combination, as well as to speculate on their mechanism. Method: A total of forty-nine adult male Sprauge-dawley rats weighing between 200 and 300 g were randomly assigned to 7 groups: sham (no Bilateral common carotid artery occlusion (BCCAO)), control group (BCCAO for 30 minutes followed by reperfusion for an hour), vehicle-1 group (rat were pretreatment with oral 1% carboxymethylcellulose for seven days followed by control group), vehicle-2 group (seven days of oral distilled water pretreatment then as control group), perindopril group (rat were pretreatment with perindopril for then as control group), coenzyme Q10 group (rat were pretreatment with coenzyme Q10 for seven days then as control group), and combination group (rat were pretreatment with perindopril plus coenzyme Q10 for seven days then as control group). The brain tissues were separated in order to measure the size of the brain infarction, assess the histology, and measure the levels of cerebral IL-6, IL-10, TNF-\(\alpha\), ICAM-1, NF-\(\kappa\)B p65, and total antioxidant capacity. Results: The brain levels of IL-6, IL-10, ICAM-1, TNF-\(\alpha\), NF-\(\kappa\)B p65, and the cerebral infarct size were substantially increased in control and vehicle in relation to sham groups, while the total anti-oxidant capacity was considerably reduced. Perindopril and coenzyme Q10 treatment alone and in combination resulted in marked elevation in IL-10 and the total antioxidant capacity, with significant decrement in IL-6, ICAM-1, TNF-\(\alpha\), and NF-\(\kappa\)B p65 in respect to vehicle and control group. There was severe histopathological ischemic damage in control and vehicle groups which was remarkedly decreased by perindopril and coenzyme Q10 treatment alone and in combination pretreatment. Conclusions: Due to their anti-inflammatory and anti-oxidative characteristics, perindopril and coenzyme Q10, either separately or in combination, exhibit neuroprotective benefits in male rats that have been treated to cerebral ischemia/reperfusion injury.