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 by vitamin E is due to its radical scavenging potency in membranes, thereby being transformed to a vitamin E radical. A deficiency of appropriate reductants, which recycle vitamin E radicals back to its antioxidative active form, causes an irreversible degradation of vitamin E leading to tocopheryl quinone (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 oxidative stress and TQ supplementation as well. Quinones in general are known to be efficient one-electron donors and acceptors. Therefore the question arises whether TQ-like compounds can undergo redox-cycling in conjunction with redox-active enzymes in the heart, thereby producing harmful oxygen radicals, or whether these compounds exhibit antioxidant properties. In order to elucidate this question we focused our interest on the interaction of TQ and a corresponding short-chain homologue (TQ(0)) with xanthine oxidase and heart 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(0) was univalently reduced by xanthine oxidase (XOD) yielding semiquinone radicals in the absence of oxygen. However, under aerobic conditions TQ(0) enhanced the O(2)(*)(-) radical output of XOD. In the mitochondrial respiratory chain TQ was shown to interact with high potential cytochrome b in the bc(1) 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 interaction with b-cytochromes in the mitochondrial respiratory chain. In isolated rat hearts perfused with liposomes containing lipophilic TQ, it was efficiently accumulated in the heart tissue. When hearts were subjected to conditions of ischemia/reperfusion, infusion of TQ prior to ischemia significantly improved the recovery of hemodynamic parameters. Our results demonstrate that TQ derivatives may induce pro-oxidative and antioxidative effects depending on the distribution of TQ derivatives in the heart tissue and the interacting redox system.
Gille
L
L
Institute of Pharmacology and Toxicology, Veterinary University Vienna, Vienna, Austria. lars.gille@vu-wien.ac.at
Staniek
K
K
Nohl
H
H
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D003573:Cytochrome b Group / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D014450:Electron Transport Complex III / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008081:Liposomes; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism*
D000975:Antioxidants; D003573:Cytochrome b Group; D008081:Liposomes; D017382:Reactive Oxygen Species; D013481:Superoxides; D014810:Vitamin E; D014527:Uric Acid; D000968:Antimycin A; C002421:tocopherylquinone; D019802:Succinic Acid; D014969:Xanthine Oxidase; D014450:Electron Transport Complex III; D010100:Oxygen