TY - JOUR AB - BACKGROUND: Oxidative stress is a risk factor for distal sensorimotor polyneuropathy (DSPN). Selenoprotein P is a protein with antioxidant properties but has not been investigated in the context of DSPN. This study aimed to assess the associations between selenoprotein P and DSPN in people without and with type 2 diabetes (T2D). METHODS: Cross-sectional and prospective analyses were based on 1053 (including 217 with T2D) and 513 participants (including 79 with T2D), respectively, aged 61-82 years from the population-based KORA F4 survey. DSPN at baseline (KORA F4) and in the follow-up survey KORA FF4 was defined based on the Michigan Neuropathy Screening Instrument. Serum levels of full-length selenoprotein P were quantified by ELISA. Associations between selenoprotein P and prevalent or incident DSPN were estimated using logistic regression analysis adjusting for multiple confounders. RESULTS: Selenoprotein P levels were not associated with prevalent DSPN in the total sample. However, there was a significant interaction by diabetes status. Higher levels of selenoprotein P were associated with lower odds of prevalent DSPN in individuals without T2D (fully adjusted model: OR 0.825 [95% CI 0.682, 0.998], p=0.0476), but not in those with T2D (OR [95% CI] 1.098 [0.829, 1.454], p=0.5132; pinteraction=0.0488). Selenoprotein P levels were not associated with incident DSPN over a follow-up of 6.5 years. CONCLUSION: In individuals without T2D from the older general population, lower selenoprotein P levels were associated with a higher prevalence of DSPN. Whether the antioxidant properties of selenoprotein P are responsible for the observed associations remains to be elucidated in future research. AU - Herder, C.* AU - Saito, Y.* AU - Spagnuolo, M.* AU - Maalmi, H.* AU - Shimizu, M.* AU - Bönhof, G.J.* AU - Suzuki, K.* AU - Rathmann, W.* AU - Peters, A. AU - Roden, M.* AU - Ziegler, D.* AU - Thorand, B. AU - Takamura, T.* C1 - 71313 C2 - 56069 CY - Ste 800, 230 Park Ave, New York, Ny 10169 Usa SP - 87-95 TI - Differential associations between selenoprotein P and distal sensorimotor polyneuropathy in people with and without diabetes: KORA F4/FF4 study. JO - Free Radical Biol. Med. VL - 223 PB - Elsevier Science Inc PY - 2024 SN - 0891-5849 ER - TY - JOUR AB - Attachment of cargo molecules to lipophilic triphenylphosphonium (TPP+) cations is a widely applied strategy for mitochondrial targeting. We previously demonstrated that the vitamin E-derived antioxidant Trolox increases the levels of active mitochondrial complex I (CI), the first complex of the electron transport chain (ETC), in primary human skin fibroblasts (PHSFs) of Leigh Syndrome (LS) patients with isolated CI deficiency. Primed by this finding, we here studied the cellular effects of mitochondria-targeted Trolox (MitoE10), mitochondria-targeted ubiquinone (MitoQ10) and their mitochondria-targeting moiety decylTPP (C10-TPP+). Chronic treatment (96 h) with these molecules of PHSFs from a healthy subject and an LS patient with isolated CI deficiency (NDUFS7-V122 M mutation) did not greatly affect cell number. Unexpectedly, this treatment reduced CI levels/activity, lowered the amount of ETC supercomplexes, inhibited mitochondrial oxygen consumption, increased extracellular acidification, altered mitochondrial morphology and stimulated hydroethidine oxidation. We conclude that the mitochondria-targeting decylTPP moiety is responsible for the observed effects and advocate that every study employing alkylTPP-mediated mitochondrial targeting should routinely include control experiments with the corresponding alkylTPP moiety. AU - Bulthuis, E.P.* AU - Einer, C. AU - Distelmaier, F.* AU - Groh, L.* AU - van Emst-de Vries, S.E.* AU - van de Westerlo, E.* AU - van de Wal, M.* AU - Wagenaars, J.* AU - Rodenburg, R.J.* AU - Smeitink, J.A.M.* AU - Riksen, N.P.* AU - Willems, P.H.G.M.* AU - Adjobo-Hermans, M.J.W.* AU - Zischka, H. AU - Koopman, W.J.H.* C1 - 65552 C2 - 52735 SP - 434-446 TI - The decylTPP mitochondria-targeting moiety lowers electron transport chain supercomplex levels in primary human skin fibroblasts. JO - Free Radical Biol. Med. VL - 188 PY - 2022 SN - 0891-5849 ER - TY - JOUR AB - Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and metabolic constraints. Dependence on NADPH/H+, polyunsaturated fatty acid metabolism, and the mevalonate and glutaminolysis metabolic pathways have been implicated in this novel form of regulated necrotic cell death. Genetic studies performed in cells and mice established the selenoenzyme glutathione peroxidase (GPX4) as the key regulator of this form of cell death. Besides these genetic models, the identification of a series of small molecule ferroptosis-specific inhibitors and inducers have not only helped in the delineation of the molecular underpinnings of ferroptosis but they might also prove highly beneficial when tipping the balance between cell death inhibition and induction in the context of degenerative diseases and cancer, respectively. In the latter, the recent recognition that a subset of cancer cell lines including certain triple negative breast cancer cells and those of therapy-resistant high-mesenchymal cell state present a high dependence on this lipid make-up offers unprecedented opportunities to eradicate difficult to treat cancers. Due to the rapidly growing interest in this form of cell death, we provide an overview herein what we know about this field today and its future translational impact. AU - Seibt, T.M.* AU - Proneth, B. AU - Conrad, M. C1 - 54323 C2 - 45512 CY - 360 Park Ave South, New York, Ny 10010-1710 Usa SP - 144-152 TI - Role of GPX4 in ferroptosis and its pharmacological implication. JO - Free Radical Biol. Med. VL - 133 PB - Elsevier Science Inc PY - 2019 SN - 0891-5849 ER - TY - JOUR AB - For the first time we here present the unambiguous identification of the formyl radical ((CHO)-C-center dot) by EPR (Electron Paramagnetic Resonance) spectroscopy and mass spectrometry (MS) using DMPO (5,5-dimethyl-1-pyrroline N-oxide) as spin trap at ambient temperature without using any catalyst(s). The (CHO)-C-center dot was continuously generated by UV photolysis in closed anoxic environment from pure formaldehyde (HCHO) in aqueous solution. The isotropic hyperfine structure constants of (CHO)-C-center dot were determined as a(N)= 15.72 G and a(H) = 21.27 G. The signals were deconvoluted and split by simulation in their single adduct components: DMPO-CHO, DMPO-H and DMPO-OH. We verified our results at first using MNP (2-methyl-2-nitroso-propane) as spin trap with known literature data and then mass spectrometry. Similarly the MNP adduct components MNP-CHO, MNP-H as well as its own adduct, the MNP-2-methyl-2-propyl (MNP-MP) were deconvoluted. Due to the low signal intensities, we had to accumulate single measurements for both spin traps. Using MS we got the exact mass of the reduced (CHO)-C-center dot adduct independently confirming the result of EPR detection of formyl radical. AU - Bauer, N.A. AU - Hoque, E. AU - Wolf, M. AU - Kleigrewe, K.* AU - Hofmann, T.* C1 - 52690 C2 - 44231 CY - New York SP - 129-133 TI - Detection of the formyl radical by EPR spin-trapping and mass spectrometry. JO - Free Radical Biol. Med. VL - 116 PB - Elsevier Science Inc PY - 2018 SN - 0891-5849 ER - TY - JOUR AB - Selenium has transitioned from an environmental poison and carcinogen to an essential micronutrient associated with a broad array of health promoting effects. These beneficial effects are now accepted to be linked to its incorporation into selenoproteins, a family of rare proteins utilizing a specialized translation machinery to integrate selenium in the form of selenocysteine. Despite this recognized role, much less is known regarding the actual role of selenium in these proteins. Here, we will provide the reader with an overview of the essential role of specific selenoproteins and their link to pathology based on mouse studies and relevant mutations discovered in humans. Additionally, we will cover recent insights linking a non-interchangeable role for selenium in glutathione peroxidase 4 and its function in suppressing ferroptosis. This critical dependency ultimately generates a strong reliance on metabolic pathways that regulate selenium metabolism and its incorporation into proteins, such as the mevalonate pathway. AU - Friedmann Angeli, J.P.F.* AU - Conrad, M. C1 - 53221 C2 - 44788 CY - 360 Park Ave South, New York, Ny 10010-1710 Usa SP - 153-159 TI - Selenium and GPX4, a vital symbiosis. JO - Free Radical Biol. Med. VL - 127 PB - Elsevier Science Inc PY - 2018 SN - 0891-5849 ER - TY - JOUR AB - Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting. Mechanistically, this is mediated by the increased detoxification of ETC-derived ROS by mitochondrial antioxidant defense, principally by the superoxide dismutase 2 - thioredoxin axis. In contrast, under conditions of glucose limitation, cell death is induced preferentially in quiescent cells and is correlated with intracellular ATP depletion but not with ROS. This is related to the inability of quiescent cells to compensate for the lost mitochondrial ATP production by the upregulation of glucose uptake. Hence, elevated ROS, not the loss of mitochondrially-generated ATP, are responsible for cell death induction by ETC disruption in ample nutrients condition, e.g. in well perfused healthy tissues, where antioxidant defense imparts specificity. However, in conditions of limited glucose, e.g.in poorly perfused tumors, ETC disruption causes rapid depletion of cellular ATP, optimizing impact towards tumor-associated dormant cells. In summary, we propose that antioxidant defense in quiescent cells is aided by local glucose limitations to ensure selectivity of ETC inhibition-induced cell death. AU - Blecha, J.* AU - Novais, S.M.* AU - Rohlenova, K.* AU - Novotna, E.* AU - Lettlova, S.* AU - Schmitt, S.* AU - Zischka, H. AU - Neuzil, J.* AU - Rohlena, J.* C1 - 51678 C2 - 43398 CY - New York SP - 253-266 TI - Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death. JO - Free Radical Biol. Med. VL - 112 PB - Elsevier Science Inc PY - 2017 SN - 0891-5849 ER - TY - JOUR AU - Ingold, I. AU - Berndt, C.* AU - Schmitt, S.* AU - Doll, S. AU - Poschmann, G.* AU - Roveri, A.* AU - Peng, X.* AU - Freitas, F.P. AU - Aichler, M. AU - Jastroch, M. AU - Ursini, F.* AU - Arner, E.S.J.* AU - Fradejas-Villar, N.* AU - Schweizer, U.* AU - Zischka, H. AU - Friedmann Angeli, J.P.F. AU - Conrad, M. C1 - 52487 C2 - 44010 CY - New York SP - 24-24 TI - Selenium utilization by GPX4 was an evolutionary requirement to prevent hydroperoxide-induced ferroptosis. JO - Free Radical Biol. Med. VL - 112 PB - Elsevier Science Inc PY - 2017 SN - 0891-5849 ER - TY - JOUR AB - Vitamin E (VE) deficiency results in pronounced muscle weakness and atrophy but the cell biological mechanism of pathology is unknown. We previously showed that VE supplementation promotes membrane repair in cultured cells and that oxidants potently inhibit repair. Here we provide three independent lines of evidence that VE is required for skeletal muscle myocyte plasma membrane repair in vivo. We also show that when another lipid-directed antioxidant, glutathione peroxidase 4 (Gpx4), is genetically deleted in mouse embryonic fibroblasts, repair fails catastrophically, unless cells are supplemented with VE. We conclude that lipid-directed antioxidant activity provided by VE, and possibly also Gpx4, is an essential component of the membrane repair mechanism in skeletal muscle. This work explains why VE is essential to muscle health and identifies VE as a requisite component of the plasma membrane repair mechanism in vivo. AU - Labazi, M.* AU - McNeil, A.K.* AU - Kurtz, T.* AU - Lee, T.C.* AU - Pegg, R.B.* AU - Friedmann Angeli, J.P.F. AU - Conrad, M. AU - McNeil, P.L.* C1 - 44248 C2 - 36777 CY - New York SP - 246-253 TI - The antioxidant requirement for plasma membrane repair in skeletal muscle. JO - Free Radical Biol. Med. VL - 84 PB - Elsevier Science Inc PY - 2015 SN - 0891-5849 ER - TY - JOUR AU - Friedmann Angeli, J.P.F. AU - Proneth, B. AU - Hammond, V.J.* AU - Tyurina, Y.Y.* AU - Tyurin, V.A.* AU - O'Donnell, V.B.* AU - Kagan, V.E.* AU - Conrad, M. C1 - 46711 C2 - 37744 CY - New York SP - S77-S78 TI - Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in a therapeutically relevant mechanism. JO - Free Radical Biol. Med. VL - 76 PB - Elsevier Science Inc PY - 2014 SN - 0891-5849 ER - TY - JOUR AB - Mitochondrial uncoupling reduces reactive oxygen species (ROS) production and appears to be important for cellular signaling/protection, making it a focus for the treatment of metabolic and age-related diseases. While the physiological role of uncoupling protein 1 (UCP1) of brown adipose tissue is established for thermogenesis, the function of UCP1 for the reduction of ROS in cold exposed mice is currently under debate. Here, we investigated the role of UCP1 for mitochondrial ROS handling in the Lesser hedgehog tenrec (Echinops telfairi), a unique proto-endothermic Malagasy mammal with recently identified brown adipose tissue. We show that the reduction of ROS by UCP1 activity also occurs in BAT mitochondria of the tenrec suggesting that the anti-oxidative role of UCP1 is an ancient mammalian trait. Our analysis elucidates that the quantity of UCP1 displays strong control over mitochondrial hydrogen peroxide release while other factors, such as mild cold, nonshivering thermogenesis, oxidative capacity and mitochondrial respiration, do not correlate. Furthermore, hydrogen peroxide release of re-coupled BAT mitochondria associated with mitochondrial membrane potential. These findings led to a model of UCP1 controlling mitochondrial ROS release and, presumably, being controlled by high membrane potential, as proposed in the canonical model of "mild uncoupling", possibly protecting from oxidative stress and maintaining cellular homeostasis. Our study further promotes an ancestral and conserved role of UCP1 in prevention of oxidative stress, which occurred before UCP1 was physiologically integrated into nonshivering thermogenesis, supporting that the ancient evolutionary history of UCP1 dates back to ectothermic vertebrates. AU - Oelkrug, R.* AU - Götze, N.* AU - Meyer, C.W. AU - Jastroch, M. C1 - 32355 C2 - 34994 SP - 210-216 TI - Antioxidant properties of UCP1 are evolutionary conserved in mammals and buffer mitochondrial reactive oxygen species. JO - Free Radical Biol. Med. VL - 77 PY - 2014 SN - 0891-5849 ER - TY - JOUR AU - Beck-Speier, I. AU - Dayal, N. AU - Karg, E.W. AU - Maier, K.L. AU - Schumann, G. AU - Schulz, S. AU - Semmler, M. AU - Takenaka, S. AU - Stettmaier, K. AU - Bors, W. AU - Ghio, A.* C1 - 3493 C2 - 22651 SP - 1080-1092 TI - Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles. JO - Free Radical Biol. Med. VL - 38 PY - 2005 SN - 0891-5849 ER - TY - JOUR AB - Reduced glutathione (GSH), a major antioxidant and modulator of cell proliferation, is decreased in the bronchoalveolar lavage fluid (BALF) of cystic fibrosis (CF) patients. We previously have shown that GSH inhalation in CF patients significantly increased GSH levels in BALF and improved lung function (M. Griese et al., 2004, Am. J. Respir. Crit. Care Med. 169, 822-828). GSH depletion in vitro enhances susceptibility to oxidative stress, increases inflammatory cytokine release, and impairs T cell responses. We therefore hypothesized that an increase in GSH in BALF reduces oxidative stress, decreases inflammation, and modulates T cell responses in lungs of CF patients. BALF from 17 CF patients (median FEV1 67% (43-105%) of predicted) was assessed before and after GSH inhalation for total protein, markers of oxidative stress (8-isoprostane, myeloperoxidase, and ascorbic and uric acid), pattern of protein oxidation, prostaglandin E2 (PGE2), and proinflammatory cytokines. BALF cells were differentiated using cytospin slides, and lymphocytes were further analyzed by flow cytometry. Inhalation of GSH decreased BALF levels of PGE2 and increased CD4+ and CD8+ lymphocytes in BALF significantly but had no effect on markers of oxidative stress. BALF lymphocytes correlated positively with lung function, whereas levels of PGE2 showed an inverse correlation. The patients with the greatest improvement in lung function after GSH treatment also had the largest decline in PGE2 levels. We conclude that GSH inhalation in CF patients increases lymphocytes and suppresses PGE2 in the bronchoalveolar space. Thus, GSH primarily affected the pulmonary immune response rather than the oxidative status in CF patients. The effect of GSH inhalation on PGE2 levels and lymphocytes in CF warrants further investigation. © 2005 Elsevier Inc. All rights reserved. AU - Hartl, D.* AU - Starosta, V.* AU - Maier, K. AU - Beck-Speier, I. AU - Rebhan, C.* AU - Becker, B.F.* AU - Latzin, P.* AU - Fischer, R.* AU - Ratjen, F.* AU - Huber, R.M.* C1 - 4778 C2 - 22768 SP - 463-472 TI - Inhaled glutathione decreases PGE2 and increases lymphocytes in cystic fibrosis lungs. JO - Free Radical Biol. Med. VL - 39 IS - 4 PY - 2005 SN - 0891-5849 ER - TY - JOUR AB - Mice harboring the activity-attenuated Gpdxa-m2Neu allele and also harboring a chromosomally integrated lacZ reporter gene to study mutagenesis (pUR288) were used to demonstrate that moderate glucose 6-phosphate dehydrogenase (G6PD) deficiency causes elevated mutagenesis and endogenous oxidative stress in the spleen. G6PD-deficient spleens with a residual enzyme activity of 22% exhibited a dramatic shift in the mutational pattern of lacZ (4.6-fold increase in the prevalence of recombination mutations of lacZ) together with a 1.8-fold increase in mutant frequencies in lacZ. A concomitant 3-fold reduction in catalase activity (dependent upon NADPH) indicated that the in vivo supply of G6PD-generated NADPH was insufficient. An additional 3-fold increase in oxidized glutathione suggested that redox control was disturbed in G6PD-deficient spleens. These findings indicate that G6PD is required for limiting oxidative mutagenesis in the mouse spleen. Gpdxa-m2Neu is the first hypomorphic allele of a mouse housekeeping gene associated with elevated somatic mutagenesis in vivo AU - Felix, K.* AU - Rockwood, L.D.* AU - Pretsch, W. AU - Bornkamm, G.W. AU - Janz, S. C1 - 10178 C2 - 20940 SP - 226-232 TI - Redox imbalance and mutagenesis in spleens of mice harboring a hypomorphic allele of Gpdx(a)encoding glucose 6-phosphate dehydrogenase. JO - Free Radical Biol. Med. VL - 34 PY - 2003 SN - 0891-5849 ER - TY - JOUR AB - Mice that harbored the x-ray-induced low efficiency allele of the major X-linked isozyme of glucose-6-phospate dehydrogenase (G6PD), Gpdx(a-m2Neu), and, in addition, harbored the transgenic shuttle vector for the determination of mutagenesis in vivo, pUR288, were employed to further our understanding of the interdependence of general metabolism, oxidative stress control, and somatic mutagenesis. The Gpdx(a-m2Neu) mutation conferred moderate G6PD deficiency in hemizygous males (Gpdx(a-m2Neu/y)) displaying residual enzyme activities of 27% in red blood cells and 13% in brain (compared to wild-type controls, Gpdx(a/y) males). In spite of this mild phenotype, the brains of G6PD-deficient males exhibited a significant distortion of redox control (similar to3-fold decrease in the ratio of reduced glutathione to oxidized glutathione), a considerable accumulation of promutagenic etheno DNA adducts (similar to13-fold increase in ethenodeoxyadenosine and similar to5-fold increase in ethenodeoxycytidine), and a substantial elevation of somatic mutation rates (similar to3-fold increase in mutant frequencies in lacZ, the target and reporter gene of mutagenesis in the shuttle vector, pUR288). The mutation pattern in the brain was dominated by illegitimate genetic recombinations, a presumed hallmark of oxidative mutagenesis. These findings suggested a critical function for G6PD in limiting oxidative mutagenesis in the mouse brain. AU - Felix, K.* AU - Rockwood, L.D.* AU - Pretsch, W. AU - Nair, J.* AU - Bartsch, H.* AU - Bornkamm, G.W. AU - Janz, S.* C1 - 21966 C2 - 20490 SP - 663-673 TI - Moderate G6PD deficiency increases mutation rates in the brain of mice. JO - Free Radical Biol. Med. VL - 32 PB - Elsevier PY - 2002 SN - 0891-5849 ER - TY - JOUR AU - Herdener, M.* AU - Heigold, S.* AU - Saran, M. AU - Bauer, G.* C1 - 21558 C2 - 19683 SP - 1260-1271 TI - Target cell-derived superoxide anions cause efficiency and selectivity of intercellular induction of apoptosis. JO - Free Radical Biol. Med. VL - 29 PY - 2000 SN - 0891-5849 ER - TY - JOUR AU - Bors, W. AU - Michel, C. C1 - 21158 C2 - 19199 SP - 1413-1426 TI - Antioxidant capacity of flavanols and gallate esters: Pulse radiolysis studies. JO - Free Radical Biol. Med. VL - 27 PY - 1999 SN - 0891-5849 ER - TY - JOUR AU - Saran, M. AU - Beck-Speier, I. AU - Fellerhoff, B. AU - Bauer, G.* C1 - 21166 C2 - 19212 SP - 482-490 TI - Phagocytic killing of microorganisms by radical processes: Consequences of the reaction of hydroxyl radicals with chloride yielding chlorine atoms. JO - Free Radical Biol. Med. VL - 26 PY - 1999 SN - 0891-5849 ER - TY - JOUR AU - Beck-Speier, I. AU - Liese, J.G. AU - Belohradsky, B.H. AU - Godleski, J.J. C1 - 20116 C2 - 13292 SP - 661-668 TI - Sulfite Stimulates NADPH Oxidase of Human Neutrophils to Produce Active Oxygen Radicals Via Protein Kinase C and Ca2+/calmodulin Pathways. JO - Free Radical Biol. Med. VL - 14 PY - 1993 SN - 0891-5849 ER - TY - JOUR AU - Beck-Speier, I. AU - Liese, J.G. AU - Belohradsky, B.H. AU - Godleski, J.J. C1 - 20713 C2 - 13931 SP - 661-668 TI - Sulfite Stimulates Nadph Oxidase of Human Neutrophils to Produce Active Oxygen Radicals Via Protein Kinase C and Ca /Calmodulin Pathways. JO - Free Radical Biol. Med. VL - 14 PY - 1993 SN - 0891-5849 ER - TY - JOUR AB - Changes in the oxidative status in the soluble proteins of bronchoalveolar lavage (BAL) fluid from monkeys were examined during 26 months of individual or combined exposure to quartz dust (5 mg/m3 of DQ12) and a hyperbaric atmosphere (2.5 bar). The oxidation of BAL proteins, assumed to be an indicator for oxidative stress in the lungs, was determined by measuring the amount of carbonyl groups in their amino acid side chains. The carbonyl content of BAL proteins (nmol carbonyl/mg protein) increased steadily to a maximum value of 156% of the control after 6 months exposure to hyperbaric atmosphere, and decreased below 50% of control levels in both the quartz alone exposed group and the group exposed to quartz in combination with a hyperbaric atmosphere. The effect of quartz on the production of reactive oxygen species by BAL cells was investigated in vitro. BAL cells from healthy monkeys preincubated with quartz and stimulated with phorbolmyristate acetate (PMA) produced reduced levels of extracellular superoxide anion and intracellular hydrogen peroxide compared with PMA-only stimulated cells. Thus the lowered carbonyl content of BAL proteins in the quartz exposed groups may have resulted from reduced production of the hydrogen peroxide which is essential for carbonyl formation by phagocytes. Changes in carbonyl content of BAL protein in vivo may be a new indicator for potential subsequent lung damage. AU - Lenz, A.-G. AU - Krombach, F.P. AU - Maier, K.L. C1 - 40574 C2 - 38713 SP - 1-10 TI - Oxidative stress in vivo and in vitro: Modulation by quartz dust and hyperbaric atmosphere. JO - Free Radical Biol. Med. VL - 12 IS - 1 PY - 1992 SN - 0891-5849 ER - TY - JOUR AB - We have investigated the influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bioenergetic functions of isolated heart-mitochondria. Electron transfer and energy conservation activities were found to be decreased in the presence of very amounts of the polychlorinated biphenyl compound (1.5 nmol/mg mitochondrial protein). The effect was greatest when substrates for complex I were used. In this case coupling of oxidative phosphorylation to respiration was drastically diminished, essentially at the expense of state 3 respiration, and P/O values were found around 2 instead of 3. Succinate-related energy conservation remained practically unaffected in the presence of TCDD, suggesting an interference of the toxic compound at coupling site I. SOD plus catalase found to protect energy-linked respiration from the effect of dioxin indicating the involvement of superoxide radicals and H2O2 in the development of the observed phenomena. The present contribution provides experimental evidence on the formation of these oxygen species in the presence of TCDD. Furthermore, the site of action of TCDD is demonstrated and discussedd in relation to the oxygen radical formation observed. AU - Summer, K.-H. AU - Nohl, H. AU - de Silva, D. C1 - 17443 C2 - 10032 SP - 369-374 TI - 2,3,7,8-Tetrachlorodibenzo-p-Dioxin induced Oxygen Activation associated with Cell Respiration. JO - Free Radical Biol. Med. VL - 6 IS - 4 PB - Pergamon-Elsevier PY - 1989 SN - 0891-5849 ER - TY - JOUR AB - Spin trapping has become a valuable tool for the study of free radicals in biology and medicine. The electron spin resonance hyperfine splitting constants of spin adducts of interest in this area are tabulated. The entries also contain a brief comment on the source of the radical trapped. AU - Buettner, G.R. C1 - 41226 C2 - 36607 SP - 259-303 TI - Spin Trapping: ESR parameters of spin adducts. JO - Free Radical Biol. Med. VL - 3 IS - 4 PY - 1987 SN - 0891-5849 ER -