Free radical biology & medicine最新文献

{"title":"Does MitoSOD protect against the toxicity of paraquat toward mitochondria by acting as a superoxide dismutase mimic?","authors":"Stefan I Liochev, Irwin Fridovich","doi":"10.1016/j.freeradbiomed.2013.02.010","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.02.010","url":null,"abstract":"","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1534"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.02.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31259880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of protein decarbonylation.","authors":"Chi-Ming Wong,&nbsp;Lucia Marcocci,&nbsp;Dividutta Das,&nbsp;Xinhong Wang,&nbsp;Haibei Luo,&nbsp;Makhosazane Zungu-Edmondson,&nbsp;Yuichiro J Suzuki","doi":"10.1016/j.freeradbiomed.2013.09.005","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.09.005","url":null,"abstract":"<p><p>Ligand/receptor stimulation of cells promotes protein carbonylation that is followed by the decarbonylation process, which might involve thiol-dependent reduction (C.M. Wong et al., Circ. Res. 102:301-318; 2008). This study further investigated the properties of this protein decarbonylation mechanism. We found that the thiol-mediated reduction of protein carbonyls is dependent on heat-labile biologic components. Cysteine and glutathione were efficient substrates for decarbonylation. Thiols decreased the protein carbonyl content, as detected by 2,4-dinitrophenylhydrazine, but not the levels of malondialdehyde or 4-hydroxynonenal protein adducts. Mass spectrometry identified proteins that undergo thiol-dependent decarbonylation, which include peroxiredoxins. Peroxiredoxin-2 and -6 were carbonylated and subsequently decarbonylated in response to the ligand/receptor stimulation of cells. siRNA knockdown of glutaredoxin inhibited the decarbonylation of peroxiredoxin. These results strengthen the concept that thiol-dependent decarbonylation defines the kinetics of protein carbonylation signaling. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1126-1133"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.09.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31740279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualizing and quantifying oxidized protein thiols in tissue sections: a comparison of dystrophic mdx and normal skeletal mouse muscles.","authors":"Tomohito Iwasaki,&nbsp;Jessica Terrill,&nbsp;Tea Shavlakadze,&nbsp;Miranda D Grounds,&nbsp;Peter G Arthur","doi":"10.1016/j.freeradbiomed.2013.09.024","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.09.024","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) are not only a cause of oxidative stress in a range of disease conditions but are also important regulators of physiological pathways in vivo. One mechanism whereby ROS can regulate cell function is by modification of proteins through the reversible oxidation of their thiol groups. An experimental challenge has been the relative lack of techniques to probe the biological significance of protein thiol oxidation in complex multicellular tissues and organs. We have developed a sensitive and quantitative fluorescence labeling technique to detect and localize protein thiol oxidation in histological tissue sections. In our technique, reduced and oxidized protein thiols are visualized and quantified on two consecutive tissue sections and the extent of protein thiol oxidation is expressed as a percentage of total protein thiols (reduced plus oxidized). We tested the application of this new technique using muscles of dystrophic (mdx) and wild-type C57Bl/10Scsn (C57) mice. In mdx myofibers, protein thiols were consistently more oxidized (19 ± 3%) compared with healthy myofibers (10 ± 1%) in C57 mice. A striking observation was the localization of intensive protein thiol oxidation (70 ± 9%) within myofibers associated with necrotic damage. Oxidative stress is an area of active investigation in many fields of research, and this technique provides a useful tool for locating and further understanding protein thiol oxidation in normal, damaged, and diseased tissues.</p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1408-1416"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.09.024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31781587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endo-PDI is required for TNFα-induced angiogenesis.","authors":"Livia de Lucca Camargo,&nbsp;Andrea Babelova,&nbsp;Anja Mieth,&nbsp;Andreas Weigert,&nbsp;Juliane Mooz,&nbsp;Krishnaraj Rajalingam,&nbsp;Heinrich Heide,&nbsp;Ilka Wittig,&nbsp;Lucia Rossetti Lopes,&nbsp;Ralf P Brandes","doi":"10.1016/j.freeradbiomed.2013.09.028","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.09.028","url":null,"abstract":"<p><p>Protein disulfide isomerase (PDI) and its homologs are oxidoreductases facilitating protein folding in the ER. Endo-PDI (also termed ERp46) is highly expressed in endothelial cells. It belongs to the PDI family but its physiological function is largely unknown. We studied the role of Endo-PDI in endothelial angiogenic responses. Stimulation of human umbilical vein endothelial cells (with TNFα (10ng/ml) increased ERK1/2 phosphorylation. This effect was largely attenuated by Endo-PDI siRNA, whereas JNK and p38 MAP kinase phosphorylation was Endo-PDI independent. Similarly, TNFα-stimulated NF-κB signaling determined by IκBα degradation as well as TNFα-induced ICAM expression was unaffected by Endo-PDI siRNA. The action of Endo-PDI was not mediated by extracellular thiol exchange or cell surface PDI as demonstrated by nonpermeative inhibitors and PDI-neutralizing antibody. Moreover, exogenously added PDI failed to restore ERK1/2 activation after Endo-PDI knockdown. This suggests that Endo-PDI acts intracellularly potentially by maintaining the Ras/Raf/MEK/ERK pathway. Indeed, knockdown of Endo-PDI attenuated Ras activation measured by G-LISA and Raf phosphorylation. ERK activation influences gene expression by the transcriptional factor AP-1, which controls MMP-9 and cathepsin B, two proteases required for angiogenesis. TNFα-stimulated MMP-9 and cathepsin B induction was reduced by silencing of Endo-PDI. Accordingly, inhibition of cathepsin B or Endo-PDI siRNA blocked the TNFα-stimulated angiogenic response in the spheroid outgrowth assays. Moreover ex vivo tube formation and in vivo Matrigel angiogenesis in response to TNFα were attenuated by Endo-PDI siRNA. In conclusion, our study establishes Endo-PDI as a novel, important mediator of AP-1-driven gene expression and endothelial angiogenic function. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1398-1407"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.09.028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31789007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-related DNA damage and expression of CD133 and Oct3/4 in cholangiocarcinoma patients with poor prognosis.","authors":"Raynoo Thanan,&nbsp;Chawalit Pairojkul,&nbsp;Somchai Pinlaor,&nbsp;Narong Khuntikeo,&nbsp;Chaisiri Wongkham,&nbsp;Banchob Sripa,&nbsp;Ning Ma,&nbsp;Kulthida Vaeteewoottacharn,&nbsp;Ayako Furukawa,&nbsp;Hatasu Kobayashi,&nbsp;Yusuke Hiraku,&nbsp;Shinji Oikawa,&nbsp;Shosuke Kawanishi,&nbsp;Puangrat Yongvanit,&nbsp;Mariko Murata","doi":"10.1016/j.freeradbiomed.2013.07.034","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.07.034","url":null,"abstract":"<p><p>Nitrative and oxidative DNA damage plays an important role in inflammation-related carcinogenesis. Chronic inflammation such as parasite infection and primary sclerosing cholangitis can be an etiological factor of cholangiocarcinoma. Using a proteomic approach and double-fluorescent staining, we identified high expression and colocalization of albumin and cytokeratin-19 in liver fluke-associated cholangiocarcinoma tissues, compared with normal livers from cholangiocarcinoma patients and cadaveric donors, respectively. Albumin was detected not only in cells of hyperplastic bile ducts and cholangiocarcinoma, but also in liver stem/progenitor cell origin, such as canal of Hering, ductules, and ductular reactions, suggesting the involvement of stem/progenitor cells in cholangiocarcinoma development. To clarify the involvement of liver stem/progenitor cells in cholangiocarcinoma, we examined several stem/progenitor cell markers (CD133, CD44, OV6, and Oct3/4) in cholangiocarcinoma tissues analyzed by immunohistochemical staining, and measured 8-oxodG levels by using HPLC-ECD as an inflammation-related DNA lesion. In addition, a stem/progenitor cell factor Bmi1, 8-nitroguanine (formed during nitrative DNA damage), DNA damage response (DDR) proteins (phosphorylated ATM and γ-H2AX), and manganese-SOD (Mn-SOD) were analyzed by immunohistochemistry. Stem/progenitor cell markers (CD133, OV6, CD44, and Oct3/4) were positively stained in 56, 38, 47, and 56% of 34 cholangiocarcinoma cases, respectively. Quantitative analysis of 8-oxodG revealed significantly increased levels in CD133- and/or Oct3/4-positive tumor tissues compared to negative tumor tissues, as well as 8-nitroguanine formation detected by immunohistochemistry. In the cases of CD44- and/or OV6-positive tissue, no significant difference was observed. Cholangiocarcinoma patients with CD133- and/or Oct3/4-positive tumor tissues showed significantly lower expression of Mn-SOD and higher DDR protein, γ-H2AX. Moreover, CD133- and/or Oct3/4-positive cholangiocarcinoma patients had significant associations with tumor histology types, tumor stage, and poor prognoses. Our results suggest that CD133 and Oct3/4 in cholangiocarcinoma are associated with increased formation of DNA lesions and the DDR protein, which may be involved in genetic instability and lead to cholangiocarcinoma development with aggressive clinical features. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1464-1472"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.07.034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31634894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiplatelet effects of dietary nitrate in healthy volunteers: involvement of cGMP and influence of sex.","authors":"Shanti Velmurugan, Vikas Kapil, Suborno M Ghosh, Sheridan Davies, Andrew McKnight, Zainab Aboud, Rayomand S Khambata, Andrew J Webb, Alastair Poole, Amrita Ahluwalia","doi":"10.1016/j.freeradbiomed.2013.06.031","DOIUrl":"10.1016/j.freeradbiomed.2013.06.031","url":null,"abstract":"<p><p>Ingestion of vegetables rich in inorganic nitrate has emerged as an effective method, via the formation of a nitrite intermediate, for acutely elevating vascular NO levels. As such a number of beneficial effects of dietary nitrate ingestion have been demonstrated including the suggestion that platelet reactivity is reduced. In this study we investigated whether inorganic nitrate supplementation might also reduce platelet reactivity in healthy volunteers and have determined the mechanisms involved in the effects seen. We conducted two randomised crossover studies each in 24 (12 of each sex) healthy subjects assessing the acute effects of dietary nitrate (250 ml beetroot juice) or potassium nitrate capsules (KNO3, 8 mmol) vs placebo control on platelet reactivity. Inorganic nitrate ingested either from a dietary source or via supplementation raised circulating nitrate and nitrite levels in both sexes and attenuated ex vivo platelet aggregation responses to ADP and, albeit to a lesser extent, collagen but not epinephrine in male but not female volunteers. These inhibitory effects were associated with a reduced platelet P-selectin expression and elevated platelet cGMP levels. In addition, we show that nitrite reduction to NO occurs at the level of the erythrocyte and not the platelet. In summary, our results demonstrate that inorganic nitrate ingestion, whether via the diet or through supplementation, causes a modest decrease in platelet reactivity in healthy males but not females. Our studies provide strong support for further clinical trials investigating the potential of dietary nitrate as an adjunct to current antiplatelet therapies to prevent atherothrombotic complications. Moreover, our observations highlight a previously unknown sexual dimorphism in platelet reactivity to NO and intimate a greater dependence of males on the NO-soluble guanylate cyclase pathway in limiting thrombotic potential.</p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1521-1532"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31539188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Tocopherol administration blocks adaptive changes in cell NADH/NAD+ redox state and mitochondrial function leading to inhibition of gastric mucosa cell proliferation in rats.","authors":"Marisela Olguín-Martínez,&nbsp;Diego R Hernández-Espinosa,&nbsp;Rolando Hernández-Muñoz","doi":"10.1016/j.freeradbiomed.2013.08.176","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.08.176","url":null,"abstract":"<p><p>In experimentally induced chronic gastritis, a compensatory mucosal cell proliferation occurs with enhanced glucose oxidative metabolism linked to lipoperoxidative events. Therefore, this study was aimed at assessing the participation of cell NAD/NADH redox state and mitochondrial functions during gastric mucosa proliferation and the effects of in vivo α-tocopherol (vitamin E) administration. Glucose oxidation and oxygen consumption were tested in gastric mucosa samples obtained from rats with gastritis and from those also treated with α-tocopherol. Gastric mucosal mitochondria were isolated and structural and functional parameters were determined. Succinate oxidation, ADP phosphorylation, mitochondrial enzyme activities, and membrane lipid composition were measured. In addition, parameters indicative of cellular NAD/NADH redox state, proliferation, apoptosis, and nitric oxide (NO) metabolism were also determined. After ethanol withdrawal, the damaged gastric mucosa increased glucose and oxygen consumption, events associated with a more reduced cytoplasmic NAD/NADH ratio. Enhanced mitochondrial oxidative phosphorylation and increased mitochondrial enzyme activities occurred early, accompanied by recovery of lost mitochondrial protein and lipid composition in the gastric mucosa, events associated with increased NO production. When mitochondrial function and structural events were normalized, apoptosis was initiated as assessed by the mitochondrial Bax/Bcl2 ratio. Treatment with α-tocopherol inhibited cell proliferation and blocked enhanced glucose utilization, mitochondrial substrate oxidation, and changes in redox state, delaying the onset of these adaptive metabolic changes, whereas it inhibited cell proliferation. In conclusion, α-tocopherol could abolish damage-induced \"stress\" signaling by desynchronizing mitochondrial adaptive responses, including mitochondria biogenesis, and consequently NAD/NADH redox, which seems to regulate gastric mucosal cell proliferation. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1090-1100"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.08.176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31697808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide scavenging by red cell microparticles.","authors":"Chen Liu,&nbsp;Weixin Zhao,&nbsp;George J Christ,&nbsp;Mark T Gladwin,&nbsp;Daniel B Kim-Shapiro","doi":"10.1016/j.freeradbiomed.2013.09.002","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.09.002","url":null,"abstract":"<p><p>Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 1000 times faster than red-cell-encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles influences NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage, and the proportion of extra erythrocytic hemoglobin in the red cell microparticle fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO-scavenging ability of cell-free hemoglobin is slightly higher than that of red cell microparticles as determined by a chemiluminescence NO-scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single-microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent, and NO-dependent vasodilation. Taken together, these data suggest that as little as 5 μM hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation.</p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1164-1173"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31746856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of autophagy and glycolysis by nitric oxide during hypoxia-reoxygenation impairs cellular bioenergetics and promotes cell death in primary neurons.","authors":"Gloria A Benavides,&nbsp;Qiuli Liang,&nbsp;Matthew Dodson,&nbsp;Victor Darley-Usmar,&nbsp;Jianhua Zhang","doi":"10.1016/j.freeradbiomed.2013.09.006","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.09.006","url":null,"abstract":"<p><p>Excessive nitric oxide (NO) production is known to damage mitochondrial proteins and the autophagy repair pathway and so can potentially contribute to neurotoxicity. Accordingly, we hypothesized that protection against protein damage from reactive oxygen and nitrogen species under conditions of low oxygen by the autophagy pathway in neurons would be impaired by NO and enhance bioenergetic dysfunction. Rat primary cortical neurons had the same basal cellular respiration in hypoxia as in normoxia, whereas NO-exposed cells exhibited a gradual decrease in mitochondrial respiration in hypoxia. Upon reoxygenation, the respiration in NO-treated cells did not recover to prehypoxic levels. Hypoxia-reoxygenation in the presence of NO was associated with inhibition of autophagy, and the inability to recover during reoxygenation was exacerbated by an inhibitor of autophagy, 3-methyladenine. The effects of hypoxia could be recapitulated by inhibiting glycolytic flux under normoxic conditions. Under both normoxic and hypoxic conditions NO exposure induced immediate stimulation of glycolysis, but prolonged NO exposure, associated with irreversible inhibition of mitochondrial respiration in hypoxia, inhibited glycolysis. Importantly, we found that NO inhibited basal respiration under normoxic conditions only when glucose was absent from the medium or glycolysis was inhibited by 2-deoxy-d-glucose, revealing a novel NO-dependent mechanism for the inhibition of mitochondrial respiration that is modulated by glycolysis. Taken together these data suggest an oxygen-dependent interaction between mitochondrial respiration, glycolysis, and autophagy in protecting neuronal cells exposed to NO. Importantly, they indicate that mitochondrial dysfunction is intimately linked to a failure of glycolytic flux induced by exposure to NO. In addition, these studies provide new insights into the understanding of how autophagy and NO may play interactive roles in neuroinflammation-induced cellular damage, which is pertinent to our understanding of the pathology of neurodegenerative diseases in which excessive NO is generated. </p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1215-1228"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.09.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31750645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γ-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation.","authors":"Eunice Mah,&nbsp;Ruisong Pei,&nbsp;Yi Guo,&nbsp;Kevin D Ballard,&nbsp;Tyler Barker,&nbsp;Victoria E Rogers,&nbsp;Beth A Parker,&nbsp;Alan W Taylor,&nbsp;Maret G Traber,&nbsp;Jeff S Volek,&nbsp;Richard S Bruno","doi":"10.1016/j.freeradbiomed.2013.09.016","DOIUrl":"https://doi.org/10.1016/j.freeradbiomed.2013.09.016","url":null,"abstract":"<p><p>Oxidative stress and inflammation persist years after smoking cessation thereby limiting the restoration of vascular endothelial function (VEF). Although short-term smoking cessation improves VEF, no studies have examined co-therapy of antioxidants in combination with smoking cessation to improve VEF. We hypothesized that improvements in γ-tocopherol (γ-T) status during smoking cessation would improve VEF beyond that from smoking cessation alone by decreasing oxidative stress and proinflammatory responses. A randomized, double-blind, placebo-controlled study was conducted in otherwise healthy smokers (22 ± 1 years; mean ± SEM) who quit smoking for 7 days with placebo (n=14) or γ-T-rich supplementation (n=16; 500 mg γ-T/day). Brachial artery flow-mediated dilation (FMD), cotinine, and biomarkers of antioxidant status, oxidative stress, and inflammation were measured before and after 7 days of smoking cessation. Smoking cessation regardless of supplementation similarly decreased plasma cotinine, whereas γ-T-rich supplementation increased plasma γ-T by seven times and its urinary metabolite γ-carboxyethyl hydroxychroman by nine times (P<0.05). Smoking cessation with γ-T-rich supplementation increased FMD responses by 1.3% (P<0.05) beyond smoking cessation alone (4.1 ± 0.6% vs 2.8 ± 0.3%; mean ± SEM). Although plasma malondialdehyde decreased similarly in both groups (P<0.05), plasma oxidized LDL and urinary F2-isoprostanes were unaffected by smoking cessation or γ-T-rich supplementation. Plasma TNF-α and myeloperoxidase decreased (P<0.05) only in those receiving γ-T-rich supplements and these were inversely related to FMD (P<0.05; R=-0.46 and -0.37, respectively). These findings demonstrate that short-term γ-T-rich supplementation in combination with smoking cessation improved VEF beyond that from smoking cessation alone in young smokers, probably by decreasing the proinflammatory mediators TNF-α and myeloperoxidase.</p>","PeriodicalId":505743,"journal":{"name":"Free radical biology & medicine","volume":" ","pages":"1291-1299"},"PeriodicalIF":7.4,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.freeradbiomed.2013.09.016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31767524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}