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

Nitric oxide (NO)-donor antioxidants are a class of polyvalent drugs which is 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 activity are reported. The I/R experiments were performed on isolated rat heart preparations perfused at 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 hrs. The compounds were added to the perfusion buffer during the first 20 min of reperfusion. At the end of each experiment, infarct size was measured with nitro-blu 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.