title: Pretreatment with low-dose gadolinium chloride attenuates myocardial ischemia/reperfusion injury in rats.
abstract: OBJECTIVE
  We have shown that low-dose gadolinium chloride (GdCl3) abolishes arachidonic acid (AA)-induced increase of cytoplasmic Ca(2+), which is known to play a crucial role in myocardial ischemia/reperfusion (I/R) injury. The present study sought to determine whether low-dose GdCl3 pretreatment protected rat myocardium against I/R injury in vitro and in vivo.
  
  
  METHODS
  Cultured neonatal rat ventricular myocytes (NRVMs) were treated with GdCl3 or nifedipine, followed by exposure to anoxia/reoxygenation (A/R). Cell apoptosis was detected; the levels of related signaling molecules were assessed. SD rats were intravenously injected with GdCl3 or nifedipine. Thirty min after the administration the rats were subjected to LAD coronary artery ligation followed by reperfusion. Infarction size, the release of serum myocardial injury markers and AA were measured; cell apoptosis and related molecules were assessed.
  
  
  RESULTS
  In A/R-treated NRVMs, pretreatment with GdCl3 (2.5, 5, 10 μmol/L) dose-dependently inhibited caspase-3 activation, death receptor-related molecules DR5/Fas/FADD/caspase-8 expression, cytochrome c release, AA release and sustained cytoplasmic Ca(2+) increases induced by exogenous AA. In I/R-treated rats, pre-administration of GdCl3 (10 mg/kg) significantly reduced the infarct size, and the serum levels of CK-MB, cardiac troponin-I, LDH and AA. Pre-administration of GdCl3 also significantly decreased the number of apoptotic cells, caspase-3 activity, death receptor-related molecules (DR5/Fas/FADD) expression and cytochrome c release in heart tissues. The positive control drug nifedipine produced comparable cardioprotective effects in vitro and in vivo.
  
  
  CONCLUSIONS
  Pretreatment with low-dose GdCl3 significantly attenuates I/R-induced myocardial apoptosis in rats by suppressing activation of both death receptor and mitochondria-mediated pathways.
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Zheng
authors.affiliation: Department of Head-Neck Surgery, Beijing Cancer Hospital, Beijing 100142, China.
authors.forename: Yun-tao
authors.initials: YT
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Jing-yi
authors.initials: JY
authors.lastname: Xue
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Zheng-yang
authors.initials: ZY
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Xin-xin
authors.initials: XX
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Da-li
authors.initials: DL
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D005682:Gadolinium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D016718:Arachidonic Acid; D005682:Gadolinium; D053148:Caspase 3; C038958:gadolinium chloride