Effects of tocopheryl quinone on the heart: Model experiments with xanthine oxidase, heart mitochondria, and isolated perfused rat hearts

It is generally accepted that the protection effect of biological tissues b y vitamin E is due to its radical scavenging potency in membranes, thereby being transformed to a vitamin E radical. A deficiency of appropriate reduc tants, which recycle vitamin E radicals back to its antioxidative active fo rm, causes an irreversible degradation of vitamin E leading to tocopheryl q uinone (TQ). TQ-like compounds were shown to result from both vitamin E and corresponding hydrophilic analogues of this antioxidant in vitro. In vivo elevated concentrations of tocopheryl quinones were detected after oxidativ e stress and TQ supplementation as well. Quinones in general are known to b e efficient one-electron donors and accepters. Therefore the question arise s whether TQ-like compounds can undergo redoxcycling in conjunction with re dox-active enzymes in the heart, thereby producing harmful oxygen radicals, or whether these compounds exhibit antioxidant properties. In order to elu cidate this question we focused our interest on the interaction of TQ and a corresponding short-chain homologue (TQ(0)) with xanthine oxidase and hear t mitochondria. Furthermore, we tested the influence of TQ on the recovery of isolated perfused rat hearts after ischemia/reperfusion. Our experiments revealed that hydrophilic TQ, was univalently reduced by xanthine oxidase (XOD) yielding semiquinone radicals in the absence of oxygen. However, unde r aerobic conditions TQ, enhanced the O-2(.-) radical output of XOD. In the mitochondrial respiratory chain TQ was shown to interact with high potenti al cytochrome b in the be, complex specifically. In contrast to the system XOD/TQ(0), lipophilic TQ in submitochondrial particles decreased the O-2(.- ) radical release during regular respiration possibly due to its interactio n with b-cytochromes in the mitochondrial respiratory chain. In isolated ra t hearts perfused with liposomes containing lipophilic TQ, it was efficient ly accumulated in the heart tissue. When hearts were subjected to condition s of ischemia/reperfusion. infusion of TQ prior to ischemia significantly i mproved the recovery of hemodynamic parameters. Our results demonstrate tha t TQ derivatives may induce pro-oxidative and antioxidative effects dependi ng on the distribution of TQ derivatives in the heart tissue and the intera cting redox system. (C) 2001 Elsevier Science Inc.