title: Effects of cadmium on cardiac metallothionein induction and ischemia-reperfusion injury in rats.
abstract: Myocardial ischemia-reperfusion injury is associated with an imbalance between the formation and the scavenging of reactive oxygen species. In this context, the protective role of the antioxidant metallothionein, a thiol-rich protein that is induced in different organs in response to heavy metals and oxidative conditions, has mainly been investigated in metallothionein-knockout mice or metallothionein-overexpressing mice. The aim of this study was to evaluate whether the administration of cadmium has a protective effect against cardiac ischemia-reperfusion injury and whether this is associated with induction of in vivo cardiac metallothionein. Forty-eight hours after an injection of 0, 1, or 2 mg/kg cadmium, isolated perfused rat hearts were submitted to 30 min of total global ischemia and 30 min of reperfusion. The ischemia-reperfusion sequence was associated with a significant decrease in cardiac metallothionein levels. Pretreatment with cadmium at a dose of 2 mg/kg (i) prevented this decrease and (ii) improved the postischemic recuperation of the coronary flow, the ventricular developed pressure, and therefore, the global postischemic functional recovery. These results showed that pretreatment of rats with 2 mg/kg cadmium induced cardioprotection against ischemia-reperfusion injuries, perhaps through an in vivo metallothionein induction that may be related to a metal activation of antioxidant systems.
authors.affiliation: Laboratoire de Physiologie et de Pharmacologie, Nutrition Preventive Experimentale, 2SBP EA 4267, IFR 133, UFR SMP, Universite de Franche Comte, 25030 Besancon, France. sylvie.devaux@univ.fcomte.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Devaux
authors.forename: Véronique
authors.initials: V
authors.lastname: Maupoil
authors.forename: Alain
authors.initials: A
authors.lastname: Berthelot
mesh_terms: D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D005609:Free Radicals; D008668:Metallothionein; D019256:Cadmium Chloride