ubiquinone and 6-hydroxy-2-5-7-8-tetramethylchroman-2-carboxylic-acid

Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, antioxidants may still play a role in cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non-mitochondrial- and mitochondrial-targeted antioxidants. Utilizing mouse models of chemical hepatocarcinogenesis, we showed that administration of non-mitochondria-targeted antioxidants N-acetylcysteine (NAC) and the soluble vitamin E analog, Trolox, prevented tumorigenesis, whereas administration of mitochondria-targeted antioxidants SS-31 (the mitochondria-targeted peptide) and Mito-Q (a derivative of ubiquinone) facilitated tumorigenesis. RNA sequencing revealed that NAC and SS-31 caused very different changes in the oxidation-reduction state and DNA damage response. In diethylnitrosamine (DEN)-treated primary hepatocytes, NAC and Trolox alleviated DNA damage by activating ataxia-telangiectasia mutated (ATM)/ATM and Rad3-related (ATR) for DNA repair whereas SS-31 and Mito-Q aggravated damage by inactivating them. Interestingly, partial recovery of SS-31-scavengened mitochondrial reactive oxygen species (mtROS) could alleviate SS-31-aggravated DNA damage. Localization of ATM between mitochondria and nuclei was altered after NAC and SS-31 treatment. Furthermore, blockage of phospho-ATR (p-ATR) led to the recurrence of NAC-ameliorated DEN HCC. In contrast, reactivation of p-ATR blocked SS-31-promoted DEN HCC. Conclusion: These results demonstrate that the type of antioxidants plays a previously unappreciated role in hepatocarcinogenesis, and provide a mechanistic rationale for exploring the therapeutic use of antioxidants for liver cancer. (Hepatology 2018;67:623-635).

Topics: Acetylcysteine; Animals; Antioxidants; Ataxia Telangiectasia Mutated Proteins; Chromans; Diethylnitrosamine; DNA Repair; Liver Neoplasms, Experimental; Male; Mice; Mitochondria; Oligopeptides; Organophosphorus Compounds; Reactive Oxygen Species; Ubiquinone

Propionic acidemia (PA), caused by a deficiency of the mitochondrial biotin dependent enzyme propionyl-CoA carboxylase (PCC) is one of the most frequent organic acidurias in humans. Most PA patients present in the neonatal period with metabolic acidosis and hyperammonemia, developing different neurological symptoms, movement disorders and cardiac complications. There is strong evidence indicating that oxidative damage could be a pathogenic factor in neurodegenerative, mitochondrial and metabolic diseases. Recently, we identified an increase in ROS levels in PA patients-derived fibroblasts. Here, we analyze the capability of seven antioxidants to scavenge ROS production in PA patients' cells. Tiron, trolox, resveratrol and MitoQ significantly reduced ROS content in patients and controls' fibroblasts. In addition, changes in the expression of two antioxidant enzymes, superoxide dismutase and glutathione peroxidase, were observed in PA patients-derived fibroblasts after tiron and resveratrol treatment. Our results in PA cellular models establish the proof of concept of the potential of antioxidants as an adjuvant therapy for PA and pave the way for future assessment of antioxidant strategies in the murine model of PA.

Topics: 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; Antioxidants; Chromans; Fibroblasts; Gene Expression; Glutathione Peroxidase; Glutathione Peroxidase GPX1; Humans; Methylmalonyl-CoA Decarboxylase; Mitochondria; Mutation; Organophosphorus Compounds; Primary Cell Culture; Propionic Acidemia; Reactive Oxygen Species; Resveratrol; Stilbenes; Superoxide Dismutase; Ubiquinone

The aim of this work was to perform a pilot study on the safety and efficacy of nanoparticle formulation for cosmetic application. The encapsulated actives in the nanoparticles were a blend of coenzyme Q10, retinyl palmitate, tocopheryl acetate, grape seed oil and linseed oil. The nanoparticle suspension was characterized in terms of pH and particle size. For the safety assessment, alternative methods as cytotoxicity and HET CAM were used. The clinical skin compatibility tests were also performed. The efficacy was evaluated in healthy volunteers presenting different degrees of periorbital wrinkles. Skin hydration was performed by corneometry. The nanoparticles presented narrow size around 140 nm and pH close to neutral and were suitable to cutaneous application. The alternative tests demonstrated that the nanoparticles did not present potential to induce skin irritant effects, cytotoxicity or generate oxidative stress. The clinical assays confirmed the in vitro results, demonstrating the safety of the nanoparticles, which were not irritant, sensitizing and comedogenic. Furthermore, the exposure to UVA light did not cause photoxicity. Regarding the efficacy, nanoparticles presented significant reduction in wrinkle degree after 21 days of application compared to the control. The volunteers could differentiate the nanoparticles and the control product by means of subjective analyses. In conclusion, the nanoparticles containing antioxidant actives were safe for topical use and presented anti-aging activity in vivo and are suitable to be used as cosmetic ingredient.

Topics: Adult; Animals; Antioxidants; Cell Survival; Chickens; Chromans; Cosmetics; Diterpenes; Humans; Hydrogen-Ion Concentration; Linseed Oil; Mice; Mice, Inbred BALB C; Middle Aged; Nanoparticles; NIH 3T3 Cells; Particle Size; Retinyl Esters; Skin; Skin Aging; Skin Irritancy Tests; Sunscreening Agents; Tocopherols; Ubiquinone; Vitamin A

To investigate the neuroprotective effects of coenzyme Q10 and/or a vitamin E analogue on retinal damage both in vitro and in vivo.. We employed cultured retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus) in vitro. Cell damage was induced by 24-h hydrogen peroxide (H2O2) exposure, and cell viability was measured using tetrazolium salt (WST-8). To examine the retinal damage induced by intravitreal N-methyl-d-aspartate (NMDA) injection in mice in vivo, coenzyme Q10 at 10 mg/kg with or without alpha-tocopherol at 10 mg/kg was administered orally (p.o.) each day for 14 days, with NMDA being intravitreally injected on day 7 of this course.. In RGC-5, a combination of coenzyme Q10 and trolox, a water-soluble vitamin E analogue (a derivative of alpha-tocopherol), prevented cell damage more effectively than either agent alone. Coenzyme Q10 and alpha-tocopherol (separately or together) reduced the retinal damage, number of TUNEL-positive cells in the ganglion cell layer (GCL), and 4-hydroxyl-2-nonenal (4-HNE) expression induced by NMDA in mice in vivo.. Coenzyme Q10 and/or these vitamin E analogues exert neuroprotective effects against retinal damage both in vitro and in vivo.

Topics: Aldehydes; Animals; Antioxidants; Apoptosis; Cell Line, Transformed; Chromans; Drug Administration Routes; Drug Interactions; Excitatory Amino Acid Agonists; Hydrogen Peroxide; In Situ Nick-End Labeling; Mice; N-Methylaspartate; Oxidants; Oxidative Stress; Rats; Retina; Retinal Ganglion Cells; Ubiquinone; Vitamin E; Vitamins

We studied the influence of antioxidants (trolox, melatonin and coenzyme Q10) on 6-hydroxydopamine-induced degeneration in the substantia nigra dopaminergic neurons from the left brain hemisphere. In rats, the level of unilateral degeneration of nigrostriatal dopaminergic system was estimated on the base of an intensity of rotation movements which were contralateral to denervated hemishere and resulted from systemic injections of a dopamine receptor agonist apomorphine. It has been shown that all tested antioxidants reduced a number of animals with apomorphine-induced behavioral asymmetry in a different degree: coenzyme Q10 reduced it twofold, trolox - fivefold and melatonin - sevenfold. We suggest that a neuroprotective effects of trolox, melatonin and coenzyme Q10 are associated with their ability to block the mitochondrial pore openings in the nervous cells under exploration, and this is the way to prevent apoptotic death. An oxidative stress has been proved to take part in the apoptosis in dopamine-producing neurons in the substantia nigra, and tested antioxidants have been shown to be effective in preventing neurodegeneration.

Topics: Animals; Antioxidants; Behavior, Animal; Chromans; Disease Models, Animal; Dopamine; Male; Melatonin; Neurons; Oxidative Stress; Oxidopamine; Parkinsonian Disorders; Rats; Rats, Inbred WKY; Substantia Nigra; Ubiquinone

Amiodarone (AM), a drug used in the treatment of cardiac dysrrhythmias, can produce severe pulmonary adverse effects, including fibrosis. Although the pathogenesis of AM-induced pulmonary toxicity (AIPT) is not clearly understood, several hypotheses have been advanced, including increased inflammatory mediator release, mitochondrial dysfunction, and free-radical formation. The hypothesis that AM induces formation of reactive oxygen species (ROS) was tested in an in vitro model relevant for AIPT. Human peripheral lung epithelial HPL1A cells, as surrogates for target cells in AIPT, were susceptible to the toxicity of AM and N-desethylamiodarone (DEA), a major AM metabolite. Longer incubations (> or =6 h) of HPL1A cells with 100 microM AM significantly increased ROS formation. In contrast, shorter incubations (2 h) of HPL1A cells with AM resulted in mitochondrial dysfunction and cytoplasmic cytochrome c translocation. Preexposure of HPL1A cells to ubiquinone and alpha-tocopherol was more effective than that with Trolox C or 5,5-dimethylpyrolidine N-oxide (DMPO) at preventing AM cytotoxicity. These data suggest that mitochondrial dysfunction, rather than ROS overproduction, represents an early event in AM-induced toxicity in peripheral lung epithelial cells that may be relevant for triggering AIPT, and antioxidants that target mitochondria may potentially have beneficial effects in AIPT.

Topics: alpha-Tocopherol; Amiodarone; Anti-Arrhythmia Agents; Cell Line; Chromans; Cyclic N-Oxides; Cytochromes c; Cytoplasm; Epithelial Cells; Humans; Lung; Mitochondria; Reactive Oxygen Species; Ubiquinone

In this study, we investigated the involvement of reactive oxygen species (ROS) and calcium in staurosporine (STS)-induced apoptosis in cultured retinal neurons, under conditions of maintained membrane integrity. The antioxidants idebenone (IDB), glutathione-ethylester (GSH/EE), trolox, and Mn(III)tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly reduced STS-induced caspase-3-like activity and intracellular ROS generation. Endogenous sources of ROS production were investigated by testing the effect of the following inhibitors: 7-nitroindazole (7-NI), a specific inhibitor of the neuronal isoform of nitric oxide synthase (nNOS); arachidonyl trifluoromethyl ketone (AACOCF(3)), a phospholipase A(2) (PLA(2)) inhibitor; allopurinol, a xanthine oxidase inhibitor; and the mitochondrial inhibitors rotenone and oligomycin. All these compounds decreased caspase-3-like activity and ROS generation, showing that both mitochondrial and cytosolic sources of ROS are implicated in this mechanism. STS induced a significant increase in intracellular calcium concentration ([Ca(2+)](i)), which was partially prevented in the presence of IDB and GSH/EE, indicating its dependence on ROS generation. These two antioxidants and the inhibitors allopurinol and 7-NI also reduced the number of TdT-mediated dUTP nick-end labeling-positive cells. Thus, endogenous ROS generation and the rise in intracellular calcium are important inter-players in STS-triggered apoptosis. Furthermore, the antioxidants may help to prolong retinal cell survival upon apoptotic cell death.

Topics: Adenine; Allopurinol; Animals; Antioxidants; Apoptosis; Arachidonic Acids; Benzoquinones; Blotting, Western; Calcium; Carbon; Caspase 3; Caspases; Cell Death; Cell Survival; Chick Embryo; Chromans; Coloring Agents; Cytosol; DNA Fragmentation; Enzyme Inhibitors; Glutathione; In Situ Nick-End Labeling; Indazoles; Metalloporphyrins; Mitochondria; Neurons; Nitric Oxide Synthase; Oligomycins; Protein Isoforms; Reactive Oxygen Species; Retina; Rotenone; Staurosporine; Tetrazolium Salts; Thiazoles; Time Factors; Ubiquinone; Uncoupling Agents; Xanthine Oxidase

Superoxide activates nucleotide-sensitive mitochondrial proton transport through the uncoupling proteins UCP1, UCP2, and UCP3 (Echtay, K. S., et al. (2002) Nature 415, 1482-1486). Two possible mechanisms were proposed: direct activation of the UCP proton transport mechanism by superoxide or its products and a cycle of hydroperoxyl radical entry coupled to UCP-catalyzed superoxide anion export. Here we provide evidence for the first mechanism and show that superoxide activates UCP2 in rat kidney mitochondria from the matrix side of the mitochondrial inner membrane: (i) Exogenous superoxide inhibited matrix aconitase, showing that external superoxide entered the matrix. (ii) Superoxide-induced uncoupling was abolished by low concentrations of the mitochondrially targeted antioxidants 10-(6'-ubiquinonyl)decyltriphenylphosphonium (mitoQ) or 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (mitoVit E), which are ubiquinone (Q) or tocopherol derivatives targeted to the matrix by covalent attachment to triphenylphosphonium cation. However, superoxide-induced uncoupling was not affected by similar concentrations of the nontargeted antioxidants Q(o), Q(1), decylubiquinone, vitamin E, or 6-hydroxy-2,5,7,8-tetramethylchroman 2-carboxylic acid (TROLOX) or of the mitochondrially targeted but redox-inactive analogs decyltriphenylphosphonium or 4-chlorobutyltriphenylphosphonium. Thus matrix superoxide appears to be necessary for activation of UCP2 by exogenous superoxide. (iii) When the reduced to oxidized ratio of mitoQ accumulated by mitochondria was increased by inhibiting cytochrome oxidase, it induced nucleotide-sensitive uncoupling that was not inhibited by external superoxide dismutase. Under these conditions quinols are known to produce superoxide, and because mitoQ is localized within the mitochondrial matrix this suggests that production of superoxide in the matrix was sufficient to activate UCP2. Furthermore, the superoxide did not need to be exported or to cycle across the inner membrane to cause uncoupling. We conclude that superoxide (or its products) exerts its uncoupling effect by activating the proton transport mechanism of uncoupling proteins at the matrix side of the mitochondrial inner membrane.

Topics: Aconitate Hydratase; Animals; Antioxidants; Cations; Cell Membrane; Chromans; Cyanides; Female; Ion Channels; Kidney; Kinetics; Membrane Potentials; Membrane Transport Proteins; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins; Models, Chemical; Protein Binding; Proteins; Protons; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxides; Time Factors; Ubiquinone; Uncoupling Protein 2; Vitamin E

High affinity for NADH, and low affinity for NADPH, for reduction of endogenous coenzyme Q10 (CoQ10) by pig liver plasma membrane is reported in the present work. CoQ reduction in plasma membrane is carried out, in addition to other mechanisms, by plasma membrane coenzyme Q reductase (PMQR). We show that PMQR-catalyzed reduction of CoQ0 by both NADH and NADPH is accompanied by generation of CoQ0 semiquinone radicals in a superoxide-dependent reaction. In the presence of a water-soluble vitamin E homologue, Trolox, this reduction leads to quenching of the Trolox phenoxyl radicals. The involvement of PMQR versus DT-diaphorase under the conditions of vitamin E and selenium sufficiency and deficiency was evaluated for CoQ reduction by plasma membranes. The data presented here suggest that both nucleotides (NADH and NADPH) can be accountable for CoQ reduction by PMQR on the basis of their physiological concentrations within the cell. The enzyme is primarily responsible for CoQ reduction in plasma membrane under normal (nonoxidative stress-associated) conditions.

Topics: Animals; Antioxidants; Cell Membrane; Chromans; Coenzymes; Cytochrome c Group; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Electron Transport; Kinetics; Liver; Male; NAD; NADP; Oxidative Stress; Rats; Rats, Long-Evans; Selenium; Superoxides; Swine; Ubiquinone; Vitamin E

The recycling of Trolox, a water-soluble vitamin E homologue, by coenzyme Q0 (CoQ0) during Cu2+-initiated oxidation of ascorbate in mouse skin homogenates was investigated using electron spin resonance (ESR) spectroscopy. In a mixture containing CoQ0, Cu2+ and mouse skin homogenates, the ESR signal of CoQ0 semiquinone radical (CoQ0*-) appeared and declined with time; addition of Trolox accelerated the CoQ0*- signal decay. Only after the disappearance of the CoQ0*- signal was the appearance of the Trolox phenoxyl radical signal observed. In addition, the lifetime of the CoQ0*- signal and the length of the lag period during which the Trolox radical ESR signal could not be detected were dependent on the presence of Trolox, CoQ0 or Cu2+. The results suggest that CoQ0*-, formed by the interaction between CoQ0 and endogenous ascorbic acid (AscH-) in skin homogenates, regenerates Trolox from its phenoxyl radical.

Topics: Animals; Antioxidants; Ascorbic Acid; Chromans; Coenzymes; Copper; Electron Spin Resonance Spectroscopy; Female; Free Radicals; Kinetics; Mice; Mice, Hairless; Models, Chemical; Skin; Ubiquinone

Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. & Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products.

Topics: alpha-Linolenic Acid; Antioxidants; Butylated Hydroxytoluene; Chromans; Electron Transport; Fatty Acids, Unsaturated; Genotype; Kinetics; Lipid Peroxides; Oleic Acid; Oxidation-Reduction; Plasmids; Saccharomyces cerevisiae; Species Specificity; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Ubiquinone; Vitamin E

Male Sprague-Dawley rats were fed diets that varied qualitatively and quantitatively in antioxidants. Kidney, heart, lung, and spleen homogenates were incubated at 37 degrees C with and without hydroperoxide or Fe+2. Protection of antioxidants against oxidative damage to tissue was determined by measurement of oxidized heme proteins. Tissues from rats supplemented with dietary vitamin E and selenium showed protection compared to tissues from rats on the basal diet. Tissues from rats with diets containing larger quantities of antioxidants and both fat soluble antioxidants: vitamin E, beta-carotene, coenzyme Q10, ascorbic acid 6-palmitate and water soluble antioxidants: selenium, trolox C, acetylcysteine, coenzyme Q0, (+)-catechin, showed the highest protection.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Canthaxanthin; Carotenoids; Catechin; Chromans; Heart; Liver; Lung; Male; Myocardium; Oxidative Stress; Rats; Rats, Sprague-Dawley; Selenium; Spleen; Ubiquinone; Vitamin E

Male Sprague-Dawley rats were fed either a vitamin E and selenium deficient diet, a diet supplemented with vitamin E and selenium, or a diet supplemented with vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, Beta-carotene, canthaxanthin, coenzyme Q0, coenzyme Q10, and (+)-catechin. Rats were injected with CBrCl3 (0.05 mmol/100 g body weight) intraperitoneally. Oxidative damage to tissues was measured by formation of oxidized heme proteins (OHP) in blood, liver, kidney, heart, lung, and spleen. Diets supplemented with antioxidants showed protection against oxidative damage caused by CBrCl3. The protection was dependent on the diversity and quantity of antioxidants in the diet. In general, diets supplemented with both fat soluble and water soluble antioxidants provided better protection than diets supplemented only with vitamin E and selenium or with vitamin E, selenium, and fat soluble antioxidants.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Canthaxanthin; Carotenoids; Catechin; Chromans; Coenzymes; Heart; Hemeproteins; Kidney; Liver; Lung; Male; Myocardium; Oxidation-Reduction; Oxidative Stress; Palmitic Acid; Palmitic Acids; Rats; Rats, Sprague-Dawley; Selenium; Spleen; Ubiquinone; Vitamin E; Vitamin E Deficiency

Male SD rats were fed a vitamin E- and selenium-deficient diet, a diet supplemented with vitamin E and selenium, and diets supplemented with vitamin E, selenium, trolox C, ascorbic acid palmitate, acetylcysteine, beta-carotene, canthaxanthin, coenzyme Q0, coenzyme Q10, and (+)-catechin. Liver slices were incubated at 37 degrees C with and without CBrCl3, t-butyl-hydroperoxide, Fe+2, or Cu+2. The effect of antioxidant nutrients on the oxidative damage to rat liver was studied by measurement of the production of oxidized heme proteins (OHP) during the oxidative reactions. Diet supplemented with vitamin E and selenium showed a strong protection against heme protein oxidation compared to the antioxidant-deficient diet. Furthermore, increasing the diversity and quantity of antioxidants in the diets provided significantly more protection.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Canthaxanthin; Carotenoids; Catechin; Chromans; Dose-Response Relationship, Drug; Hemeproteins; In Vitro Techniques; Male; Oxidants; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Selenium; Ubiquinone; Vitamin D Deficiency; Vitamin E

2-Oxoglutarate-supported rat liver mitochondria were loaded with moderate amounts of calcium and submitted to O2 deprivation and reoxygenation. In the presence of acetoacetate, anaerobic energy production maintained Ca2+ retention by mitochondria during the anoxia period unless the Pi concentration of the incubation solution was raised to 4-6 mM. Acetoacetate prompted Ca2+ release from O2-deprived mitochondria at elevated Pi levels, presumably due to occurrence of a permeability transition of the inner membrane. Providing 3-hydroxybutyrate and malate, together with acetoacetate, was found to delay the permeability transition until O2 was reintroduced, i.e., O2 triggered a paradoxical release of Ca2+ from mitochondria under these conditions. Whether initiated by O2 in the presence of Pi or by Pi under aerobic conditions, Ca2+ release was initially activated and subsequently inhibited or reversed in the presence of alpha-tocopherol (10-90 mumol.g protein-1). Similar effects were exerted by alpha-tocopherol during Pi-induced Ca2+ release from oligomycin-treated mitochondria supported by succinate (+ rotenone). In addition, the permeability transition was delayed by retinol (3-30 mumol.g protein-1) while beta-carotene, ubiquinone, and water-soluble antioxidants, including Trolox C, were ineffective. Other observations suggest that the Ca(2+)-releasing and/or -retaining effects of alpha-tocopherol and retinol may be independent from pro- and/or antioxidant activities. Effects resembling those of alpha-tocopherol were exerted by alpha-tocopherol succinate, which is devoid of antioxidant activity. Our data indicate that the permeability transition of Ca(2+)-loaded liver mitochondria may be triggered by O2, in the presence of ketone bodies, and affected by lipid-soluble antioxidants through mechanisms seemingly unrelated to free-radical generation or scavenging.

Topics: Acetoacetates; Anaerobiosis; Animals; Antioxidants; beta Carotene; Calcium; Carotenoids; Chromans; Hypoxia; Kinetics; Mitochondria, Liver; Oligomycins; Oxygen; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Ubiquinone; Vitamin A; Vitamin E