Aims: Mitochondrial dysfunction is a major player in initiating the cellular cascades which lead to neuronal damage post cerebral ischemia. Angiotensin II Type 1 (AT1) receptor blockers are one of the most commonly employed antihypertensive drugs due to their good safety and efficacy profiles. This study was designed to investigate the neuroprotective potential of a newer AT1 receptor blocker azilsartan against global cerebral ischemia induced brain injury in Wistar rats and the possible involvement of mitochondrial restorative mechanism in its effect.
Methods: Bilateral common carotid artery occlusion (30min Ischemia and 48hr reperfusion) was performed in Wistar rats for the induction of global cerebral ischemia. Pre-treatment with azilsartan (2 and 4 mg/kg; p.o.) or coenzyme Q10 (20 and 40 mg/kg; p.o.) starting 7 days prior to BCCAO till the end of reperfusion was done.
Results: Azilsartan and coenzyme Q10 preserved the behavioral function (locomotor activity, rota rod performance and beam balance score), arrested oxidative stress (LPO, nitrite, GSH and SOD), decreased apoptotic damage (caspase-3), neuroinflammation (TNF-α), infarct area (TTC staining) and restored histological alterations (H&E staining) as compared to vehicle treatment. Maximum effect was seen when a combination of both drugs was administered. In addition, azilsartan was able to protect the activity of mitochondrial complexes and in combination with the ubiquitous electron carrier coenzyme Q10, it significantly preserved the mitochondrial respiratory function by stimulating the oxidative phosphorylation (oxygen consumption using clarke's electrode).
Conclusions: These findings explicitly highlight neuroprotective properties of azilsartan against cerebral ischemia, possibly through mitochondrial mechanisms.
Keywords: Azilsartan; Coenzyme Q10; Ischemia; Mitochondria; Neuroprotection; Stroke.
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