Abstract
Myocardial ischemia-reperfusion injury (IRI) is one of the most leading concerns for public health globally. Diazepam, a local anesthetic, has been reported for its cardioprotective potential. The present investigation aimed to evaluate the possible mechanism of action of diazepam against left anterior descending ligation-induced myocardial IRI in experimental rats. IRI was induced in healthy male rats by ligating coronary artery for 30 min and then reperfused for 60 min. The animals were pre-treated with either vehicle or diltiazem (10 mg/kg) or diazepam (1, 2.5, and 5 mg/kg) for 14 days. Compared to the IRI group, diazepam (2.5 and 5 mg/kg) markedly (P<0.05) attenuated IRI-induced alterations in cardiac function and oxido-nitrosative stress. In addition, diazepam prominently (P<0.05) improved cardiac Na+K+ATPase, Ca2+ATPase levels and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expression. It also significantly (P<0.05) down-regulated cardiac mRNA expressions of cardiac troponin I (cTn-I), C-C chemokine receptor type 2 (CCR2), tumor necrosis factor-alpha (TNF-α), interleukins (IL)-1β, and IL-6. In western blot analysis, IRI-induced myocardial apoptosis was reduced by diazepam treatment reflected by a marked (P<0.05) decreased in Bcl-2-associated X protein (Bax) and Caspase-3 protein expression. Diazepam also efficiently (P<0.05) improved IRI-induced histological aberration in cardiac tissue. In conclusion, diazepam exerts cardioprotective effect by inhibiting inflammatory release (CCR2, TNF-α, and ILs), oxido-nitrosative stress, and apoptosis (Bax and Caspase-3) pathway during myocardial IRI in experimental rats.