PROTECTIVE ROLE OF CHRONIC UBIQUINONE ADMINISTRATION ON ACUTE CARDIACOXIDATIVE STRESS

Previous studies have shown that acute exogenous administration of coe nzyme ubiquinone (CoQ(10)) can protect the heart against oxidant-media ted injury. The aim of this study was to investigate whether protectio n against cardiac oxidative stress could be obtained by increasing tis sue levels of CoQ(10), as achieved by chronic CoQ(10) supplementation. Wistar rats were randomly divided into two groups: a control group gi ven standard diet and a test group receiving diet supplemented with Co Q(10) (5 mg/kg/day) for 4 weeks. Functional and metabolic changes indu ced by oxidative stress were investigated in isolated perfused hearts and in papillary muscles. Tissue concentrations of ubiquinones were si gnificantly higher in the left ventricle of treated rats than in contr ols. H2O2 infusion (60 mu M for 60 min) induced marked alterations of both developed pressure, which decreased to -58.8+/-16.8% of base line and end-diastolic pressure which increased almost 13-fold. These effe cts were reduced significantly (P < .05) in hearts from CoQ(10)-supple mented rats (-13.8+/-2.3 and +375.0+/-42.5%, respectively). In the sam e hearts, cumulative release of oxidized glutathione (a specific marke r of oxidative stress) was 450.2+/-69.2 nmol/g of wet weight in the co ntrol group and only 89.6+/-22.3 nmol/g of wet weight in treated heart s (P < .01). In papillary muscles, after 60 min of perfusion with H2O2 , active tension decreased, largely in controls whereas it was almost unchanged in the treated group (-34.4+/-7.5% of baseline vs. -0.1+/-0. 05%, P < .05). Resting tension also showed a remarkable increase in pa pillary muscles of the control group with respect to treated ones (+60 0.5+/-72.7% vs. +20.3+/-6.7%, P < .005). Action potential duration was reduced in control with respect to treated hearts, reaching a maximum difference at 60 min (-51.4+/-8.4% of baseline and -0.1+/-0.03, P < . 05), whereas amplitude showed a progressive reduction in control with respect to treated papillary muscles (-5.6+/-1.3% and -0.1+/-0.02; P < .05). These effects were a specific consequence on oxidant injury, be cause inotropic and chronotropic responses to isoproterenol were not d ifferent between control and CoQ(10)-pretreated rats. Thus, our data d emonstrate that chronic dietary supplementation of CoQ(10) reduces car diac injury produced by H2O2, as assessed by several indices. The mark ed reduction observed in oxidized glutathione release suggests that th is protective action may occur via an antioxidant effect of increased tissue concentrations of ubiquinone.