Arzneimittelforschung 2009; 59(3): 111-116
DOI: 10.1055/s-0031-1296372
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Effects of Nitric Oxide Donor Antioxidants Containing the Phenol Vitamin E Substructure and a Furoxan Moiety on Ischemia/Reperfusion Injury

Antonella Di Stilo
1   Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, (Italy)
,
Konstantin Chegaev
1   Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, (Italy)
,
Loretta Lazzarato
1   Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, (Italy)
,
Roberta Fruttero
1   Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, (Italy)
,
Alberto Gasco
1   Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, (Italy)
,
Raffaella Rastaldo
2   Dipartimento di Neuroscienze, Sezione di Fisiologia, University of Torino, Torino, (Italy)
,
Sandra Cappello
2   Dipartimento di Neuroscienze, Sezione di Fisiologia, University of Torino, Torino, (Italy)
› Author Affiliations
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Publication History

Publication Date:
13 December 2011 (online)

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Abstract

Nitric oxide (NO) donor antioxidants are a class of polyvalent drugs which is the focus of great interest today. They are potentially useful for the treatment of many forms of cardiovascular diseases, including the myocardial ischemia/reperfusion (I/R) damage which seems to be due to both a burst of reactive oxygen species (ROS) and a reduced release of NO during reperfusion. In this paper the results of a study on the ability of new NO-donor antioxidants containing the phenol vitamin E substructure and furoxan moiety to attenuate I/R damage are reported. The compounds under study are obtained by combining the phenol moiety (6-hydroxy-2,2,5,7,8-pentamethylchroman) present in vitamin E with differently substituted furoxan substructures endowed with different capacity of NO-release. Their antioxidant and NO-dependent vasodilator activities are reported. The I/R experiments were performed on isolated rat heart preparations perfused at a constant flow. After 20 min of stabilization, global ischemia was obtained by interrupting the perfusion for 30 min. After ischemia the hearts were reperfused for 2 h. The compounds were added to the perfusion buffer during the first 20 min of reperfusion. At the end of each experiment, the infarct size was measured with nitro-blue tetrazolium. From the results it appears that the limitation of the infarct area is favoured by an appropriate balance between NO-donor and antioxidant properties and that these two actions are synergic.