Effects of nitric oxide donor antioxidants containing the phenol vitamin E substructure and a furoxan moiety on ischemia/reperfusion injury.
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.
Di Stilo
Antonella
A
Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, Italy. antonella.distilo@unito.it
Chegaev
Konstantin
K
Lazzarato
Loretta
L
Fruttero
Roberta
R
Gasco
Alberto
A
Rastaldo
Raffaella
R
Cappello
Sandra
S
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002021:Buffers; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology*; D009580:Nitroblue Tetrazolium; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology*
D000975:Antioxidants; D002021:Buffers; D007202:Indicators and Reagents; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D014665:Vasodilator Agents; C010166:furoxans; D014810:Vitamin E; D009580:Nitroblue Tetrazolium