Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability.
An isolated rabbit heart Langendorff preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 micrograms/ml procyanidines dose-dependently reduced ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%), decreased coronary perfusion pressure (CPP), improved cardiac mechanical performance upon reperfusion, increased the release of 6-keto-PGF1 alpha into the perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200 micrograms/ml), and suppressed rhythm irregularity. This antiarrhythmogenic action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/ min). The cardioprotective agent allopurinol infused at 20 micrograms/ml had effects on the contractility and on the release of 6-keto-PGF1 alpha comparable to those of 200 micrograms/ml procyanidines. The results of the second part of this study show that procyanidines are potent scavengers of several reactive oxygen species involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64 microM: rate constant K = 7.55 x 10(5) M-1 s-1, determined by the phenazine methosulfate/NADH method); the hydroxyl radical (IC50 = 28 microM; rate constant K = 1.2 x 10(12) M-1 s-1, determined by the electron spin resonance spectroscopy); peroxyl radicals (IC50 = 0.025 microM and 0.35 microM, determined using two different lipid substrates, phosphatidylcholine liposomes and methyl linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to strong complexes, with stability constants (log K) ranging from 9.35 to approximately 9.
Maffei Facinó
R
R
Istituto Chimico Farmaceutico Tossicologico, Milan, Italy.
Carini
M
M
Aldini
G
G
Berti
F
F
Rossoni
G
G
Bombardelli
E
E
Morazzoni
P
P
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D044946:Biflavonoids; D002317:Cardiovascular Agents / Q000494:pharmacology; D002392:Catechin / Q000302:isolation & purification / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D006321:Heart / Q000187:drug effects*; D007501:Iron / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D044945:Proanthocyanidins; D011817:Rabbits; D012639:Seeds / Q000737:chemistry
D000975:Antioxidants; D044946:Biflavonoids; D002317:Cardiovascular Agents; D016166:Free Radical Scavengers; D044945:Proanthocyanidins; C017674:procyanidin; D003300:Copper; D002392:Catechin; D011464:Epoprostenol; D007501:Iron