title: Protective effects of crocetin pretreatment on myocardial injury in an ischemia/reperfusion rat model.
abstract: Crocetin is one of the major active constituents of saffron extract, and it is a carotenoid compound that prevents reactive oxygen species and has anti-inflammation and anti-apoptosis characteristics. This study aims to investigate whether crocetin repairs myocardial damage in vivo after ischemia reperfusion (I/R) and the mechanisms underlying its cardioprotective effects. Male Wistar rats were randomly allocated into three groups: Sham, I/R, CRO. Crocetin (50mg/kg/day, i.g.) or sodium carboxymethylcellulose (CMC-Na) was intragastrically administered to Wistar rats for 7 days before operation. Myocardial ischemia reperfusion injury (MIRI) was induced by occluding the left anterior descending (LAD) coronary artery for 45min and subsequent reperfusion for 3h. The cardioprotective effects of crocetin were evaluated by biochemical values, histopathological observations and the antiapoptotic relative proteins and gene expressions. In the rat model, pretreatment with 50mg/kg crocetin reduced the cardiac injury, oxidative stress and inflammation compared with that of the non-treated rats, as shown by the decreased levels of infarct size, creatine kinase-MB (CK-MB), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) activity and the increased levels of total superoxide dismutase (T-SOD) and inflammation cytokines interleukin-10 (IL-10) activity. Crocetin activation also decreases the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining positive percentage and Bax expression, elevated Bcl-2 and endothelial nitric oxide synthase (eNOS) expression and nitrite (NO) production, these indicating that crocetin can suppress the apoptosis damage. These results indicate that crocetin can provide protection against MIRI in rats by inhibiting ROS production, blocking inflammation, and reducing myocardium apoptosis.
authors.affiliation: Department of Cardiology, The Yantai Affiliated Hospital of Binzhou Medical University, Shandong, Yantai 264100, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Yantai Affiliated Hospital of Binzhou Medical University, Shandong, Yantai 264100, China. Electronic address: bysjwu@gmail.com.
authors.forename: Jingwu
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Binzhou Medical University, Shandong, Binzhou 256603, China.
authors.forename: Chengxia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Yantai Affiliated Hospital of Binzhou Medical University, Shandong, Yantai 264100, China.
authors.forename: Can
authors.initials: C
authors.lastname: Fang
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002338:Carotenoids / Q000008:administration & dosage*; D004195:Disease Models, Animal; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D002316:Cardiotonic Agents; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids
keywords: Apoptosis; Crocetin; Inflammation; Ischemia reperfusion injury; Oxidative stress