Previous studies have shown that acute exogenous administration of coenzyme ubiquinone (CoQ10) can protect the head against oxidant-mediated injury. The aim of this study was to investigate whether protection against cardiac oxidative stress could be obtained by increasing tissue levels of CoQ10, as achieved by chronic CoQ10 supplementation.Wistar rats were randomly divided into two groups: a control group given standard diet and a test group receiving diet supplemented with CoQ10 (5 mg/kg/day) for 4 weeks. Functional and metabolic changes induced by oxidative stress were investigated in isolated perfused hearts and in papillary muscles. Tissue concentrations of ubiquinones were significantly higher in the left ventricle of treated rats than in controls. H2O2 infusion (60 μM 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 effects were reduced significantly (P <.05) in hearts from CoQ10-supplemented rats (-13.8 ± 2.3 and +375.0 ± 42.5%, respectively). In the same hearts, cumulative release of oxidized glutathione (a specific marker of oxidative stress) was 450.2 ± 69.2 nmol/g of wet weight in the control group and only 89.6 ± 22.3 nmol/g of wet weight in treated heads (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 papillary muscles of the control group with respect to treated ones (+600.5 ± 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, because inotropic and chronotropic responses to isoproterenol were not different between control and CoQ10-protracted rats. Thus, our data demonstrate that chronic dietary supplementation of CoQ10 reduces cardiac injury produced by H2O2, as assessed by several indices. The marked reduction observed in oxidized glutathione release suggests that this protective action may occur via an antioxidant effect of increased tissue concentrations of ubiquinone.
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1995|
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