Diazepam ameliorated myocardial ischemia-reperfusion injury via inhibition of C-C chemokine receptor type 2/tumor necrosis factor-alpha/interleukins and Bcl-2-associated X protein/caspase-3 pathways in experimental rats.

Content Provider	Europe PMC
Author	JIANG, Tingting MA, Xinghua CHEN, Huimin JIA, Hongfeng XIONG, Ying
Copyright Year	2021
Abstract	Myocardial ischemia-reperfusion injury (IRI) is one of the most leading concerns forpublic health globally. Diazepam, a local anesthetic, has been reported for itscardioprotective potential. The present investigation aimed to evaluate the possiblemechanism of action of diazepam against left anterior descending ligation-inducedmyocardial IRI in experimental rats. IRI was induced in healthy male rats by ligatingcoronary artery for 30 min and then reperfused for 60 min. The animals were pre-treatedwith 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 andoxido-nitrosative stress. In addition, diazepam prominently (P<0.05)improved cardiac Na+K+ATPase, Ca2+ATPase levels andhypoxia-inducible factor-1 alpha (HIF-1α) mRNA expression. It also significantly(P<0.05) down-regulated cardiac mRNA expressions of cardiac troponinI (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 apoptosiswas reduced by diazepam treatment reflected by a marked (P<0.05)decreased in Bcl-2-associated X protein (Bax) and Caspase-3 protein expression. Diazepamalso efficiently (P<0.05) improved IRI-induced histological aberrationin cardiac tissue. In conclusion, diazepam exerts cardioprotective effect by inhibitinginflammatory release (CCR2, TNF-α, and ILs), oxido-nitrosative stress, and apoptosis (Baxand Caspase-3) pathway during myocardial IRI in experimental rats.
ISSN	09167250
Volume Number	83
PubMed Central reference number	PMC8762406
Issue Number	12
PubMed reference number	34719607
Journal	The Journal of Veterinary Medical Science [J. Vet. Med. Sci]
e-ISSN	13477439
DOI	10.1292/jvms.21-0344
Language	English
Publisher	The Japanese Society of Veterinary Science
Publisher Date	2021-11-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the CreativeCommons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0:https://creativecommons.org/licenses/by-nc-nd/4.0/) ©2021 The Japanese Society of Veterinary Science
Subject Keyword	apoptosis C-C chemokine receptor type 2 cardiac troponin I diazepam ischemia-reperfusion injury
Content Type	Text
Resource Type	Article
Subject	Veterinary