Effects of pre-treatment with metoprolol and diltiazem on cerebral ischemia/reperfusion-induced injuries

Abstract

Stroke is one of the most important health concerns worldwide. Calcium ions accumulation in the nerve cells and increase in the catecholamines level of the brain following cerebral ischemia/reperfusion (I/R) are accompanied by damaging effects. Therefore, the present study aimed to evaluate the effects of diltiazem, as a calcium channel blocker, and metoprolol, as a β-adrenoceptors antagonist, on I/R injury. In this study, 30 male Wistar rats were divided into control, I/R, metoprolol, diltiazem, and metoprolol plus diltiazem groups (n=6 in each). Metoprolol (1 mg/kg/day) and diltiazem (5 mg/kg/day) were injected intraperitoneally (i.p.) for 7 days before I/R induction. On day 8, the animals underwent ischemia by bilateral common carotid arteries occlusion for 20 min. Histopathological analysis showed a significant reduction in leukocyte infiltration in diltiazem, metoprolol, and diltiazem plus metoprolol treated rats compared with the I/R group (P<0.05, P<0.01, P<0.01, respectively). In addition, in all treated groups, myeloperoxidase activity and malondialdehyde levels in the brain tissue significantly declined compared with the I/R group (P<0.001). Furthermore, pre-treatment with diltiazem and metoprolol alone or in coadministration remarkably reduced infarct size following I/R (P<0.001). Overall, the results indicate the considerable neuroprotective effects of metoprolol and diltiazem in cerebral I/R.

Protective Effect of Peptide Calcium Channel Blocker Omega-Hexatoxin-Hv1a on Epithelial Cell during Ischemia–Reperfusion Injury

“…These include derivatives of phenylalkylamine (verapamil), benzothiazepine (diltiazem), dihydropyridine (nifedipine), and others. A number of studies have shown that the use of verapamil, diltiazem or nifedipine also alleviate experimental ischemic and reperfusion injury of various organs by reducing cellular permeability to calcium [ 13 , 14 , 15 ]. However, these drugs have several limitations.…”