title: Vitamin E analogues reduce the incidence of ventricular fibrillations and scavenge free radicals.
abstract: The aim of our study was to analyse the protective effects of different alpha-tocopherol analogues 1) against fibrillations induced by an ischemia-reperfusion sequence, and 2) to further investigate in vitro the radical scavenging properties of these analogues by two sensitive methods. Concerning 1: isolated rat hearts underwent 10 min of coronary ligation followed by reperfusion and the alpha-tocopherol analogues were infused 15 min before occlusion. Functional parameters including heart rate and fibrillations were recorded. Concerning 2: the beta-phycoerythrin assay was utilised to determine the oxygen radical absorbing capacity (ORAC) of these vitamin E analogues against peroxyl radicals. Electron paramagnetic resonance (EPR) was used to measure their scavenger abilities on hydroxyl radical and superoxide anion production. Concerning 1: ventricular fibrillation times were reduced for all analogues treated hearts at concentrations of 1 microM and 5 microM, with Trolox being the most efficacious. Concerning 2: in our experimental conditions of intense production of free radicals, scavenging IC50 values for hydroxyl radical were 1.15, 2.17 and 4.04 mM for Trolox, MDL 74270 and MDL 74366 respectively. Superoxide anion IC50 values were 1.0 and 6.75 mM for Trolox and MDL 74270. Our results show that water-soluble analogues of vitamin E are effective in the prevention of coronary ligation induced reperfusion arrhythmia, under our experimental conditions. Moreover, our data demonstrate that these vitamin E analogues are effective scavengers for a variety of radicals. Our studies support the view that compounds that can either inhibit the formation or scavenge free radicals can protect the heart against arrhythmia associated with ischemia-reperfusion.
authors.affiliation: Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaires Expérimentales, Facultés de Médecine et de Pharmacie, Dijon, France.
authors.forename: M K
authors.initials: MK
authors.lastname: Walker
authors.forename: C
authors.initials: C
authors.lastname: Vergely
authors.forename: S
authors.initials: S
authors.lastname: Lecour
authors.forename: C
authors.initials: C
authors.lastname: Abadie
authors.forename: V
authors.initials: V
authors.lastname: Maupoil
authors.forename: L
authors.initials: L
authors.lastname: Rochette
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D001578:Benzopyrans / Q000627:therapeutic use; D002839:Chromans / Q000627:therapeutic use; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010799:Phycoerythrin / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000188:drug therapy*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D002839:Chromans; D016166:Free Radical Scavengers; D010799:Phycoerythrin; D013481:Superoxides; C064728:MDL 74270; C069478:MDL 74366; D014810:Vitamin E; D017665:Hydroxyl Radical; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid