title: Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure.
abstract: This study was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L. (Saffron) against subchronic diazinon (DZN) induced cardiotoxicity in rats.
  
  
  METHODS
  Rats were divided into 7 groups; control (corn oil, gavage), DZN (15 mg/kg/day, gavage,), crocin (12.5, 25 or 50 mg/kg/day, i.p) plus DZN, vitamin E (200 IU/kg, i.p, three times per week) plus DZN and crocin (50 mg/kg/day, i.p) groups. Treatments were continued for 4 weeks. Creatine phosphokinase MB (CK-MB), malondealdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. Levels of apoptotic proteins (Bax, Bcl2, caspase 3) and cytosolic cytochrome c were analyzed by Western blotting. Transcript levels of Bax and Bcl2 were also determined using qRT PCR.
  
  
  RESULTS
  DZN induced histophatological damages and elevated the level of cardiac marker CK-MB. These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax/Bcl2 ratio (both protein and mRNA levels), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue. Crocin (25 and 50 mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. In summary, DZN induced mitochondrial-mediated apoptosis in heart tissue of rat following subchronic exposure. Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis.
authors.affiliation: Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bibi Marjan
authors.initials: BM
authors.lastname: Razavi
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinzadeh
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Movassaghi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Imenshahidi
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002338:Carotenoids / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D027622:Crocus / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D003976:Diazinon / Q000633:toxicity*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D007306:Insecticides; D010936:Plant Extracts; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D002338:Carotenoids; D008315:Malondialdehyde; C029036:crocin; D045304:Cytochromes c; D003402:Creatine Kinase; D005978:Glutathione; D003976:Diazinon