{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:59:05Z","timestamp":1789559945471,"version":"build-2803163510"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T00:00:00Z","timestamp":1447372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T00:00:00Z","timestamp":1447372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Overproduction of hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) causes oxidative stress and is the main culprit in the pathogenesis of ischemia\/reperfusion (I\/R) injury. Suppression of oxidative stress is therefore critical in the treatment of I\/R injury. Here, we report H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -activatable antioxidant prodrug (BRAP) that is capable of specifically targeting the site of oxidative stress and exerting anti-inflammatory and anti-apoptotic activities. BRAP with a self-immolative boronic ester protecting group was designed to scavenge H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and release HBA (\n                    <jats:italic>p<\/jats:italic>\n                    -hydroxybenzyl alcohol) with antioxidant and anti-inflammatory activities. BRAP exerted potent antioxidant and anti-inflammatory activity in lipopolysaccharide (LPS)- and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -stimulated cells by suppressing the generation of ROS and pro-inflammatory cytokines. In mouse models of hepatic I\/R and cardiac I\/R, BRAP exerted potent antioxidant, anti-inflammatory and anti-apoptotic activities due to the synergistic effects of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -scavenging boronic esters and therapeutic HBA. In addition, administration of high doses of BRAP daily for 7 days showed no renal or hepatic function abnormalities. Therefore BRAP has tremendous therapeutic potential as H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -activatable antioxidant prodrug for the treatment of I\/R injuries.\n                  <\/jats:p>","DOI":"10.1038\/srep16592","type":"journal-article","created":{"date-parts":[[2015,11,13]],"date-time":"2015-11-13T05:28:55Z","timestamp":1447392535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Hydrogen peroxide-activatable antioxidant prodrug as a targeted therapeutic agent for ischemia-reperfusion injury"],"prefix":"10.1038","volume":"5","author":[{"given":"Dongwon","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunggyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soochan","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahee","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wooyoung","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Samad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingen","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilson","family":"Khang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,13]]},"reference":[{"key":"BFsrep16592_CR1","doi-asserted-by":"publisher","first-page":"21316","DOI":"10.1073\/pnas.1012864107","volume":"107","author":"GC Van de Bittner","year":"2010","unstructured":"Van de Bittner, G. C., Dubikovskaya, E. A., Bertozzi, C. R. & Chang, C. J. In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter. Proc Natl Acad Sci USA 107, 21316\u201321321 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep16592_CR2","doi-asserted-by":"publisher","first-page":"16652","DOI":"10.1021\/ja054474f","volume":"127","author":"EW Miller","year":"2005","unstructured":"Miller, E. W., Albers, A. E., Pralle, A., Isacoff, E. Y. & Chang, C. J. Boronate-based fluorescent probes for imaging cellular hydrogen peroxide. J Am Chem Soc 127, 16652\u201316659 (2005).","journal-title":"J Am Chem Soc"},{"key":"BFsrep16592_CR3","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1021\/bc200141h","volume":"22","author":"EA Mahmoud","year":"2011","unstructured":"Mahmoud, E. A., Sankaranarayanan, J., Morachis, J. M., Kim, G. & Almutairi, A. Inflammation Responsive Logic Gate Nanoparticles for the Delivery of Proteins. Bioconjugate Chem 22, 1416\u20131421 (2011).","journal-title":"Bioconjugate Chem"},{"key":"BFsrep16592_CR4","doi-asserted-by":"publisher","first-page":"15758","DOI":"10.1021\/ja303372u","volume":"134","author":"CD Lux","year":"2012","unstructured":"Lux, C. D. et al. Biocompatible Polymeric Nanoparticles Degrade and Release Cargo in Response to Biologically Relevant Levels of Hydrogen Peroxide. J Am Chem Soc 134, 15758\u201315764 (2012).","journal-title":"J Am Chem Soc"},{"key":"BFsrep16592_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20061131","volume":"401","author":"B Halliwell","year":"2007","unstructured":"Halliwell, B. Oxidative stress and cancer: have we moved forward? Biochem J 401, 1\u201311 (2007).","journal-title":"Biochem J"},{"key":"BFsrep16592_CR6","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6","volume":"190","author":"DL Carden","year":"2000","unstructured":"Carden, D. L. & Granger, D. N. Pathophysiology of ischaemia-reperfusion injury. J Pathol 190, 255\u2013266 (2000).","journal-title":"J Pathol"},{"key":"BFsrep16592_CR7","doi-asserted-by":"publisher","first-page":"2B","DOI":"10.1016\/0002-9149(94)90257-7","volume":"73","author":"MO Jeroudi","year":"1994","unstructured":"Jeroudi, M. O., Hartley, C. J. & Bolli, R. Myocardial reperfusion injury: role of oxygen radicals and potential therapy with antioxidants. Am J Cardiol 73, 2B\u20137B (1994).","journal-title":"Am J Cardiol"},{"key":"BFsrep16592_CR8","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/S0967-2109(02)00070-4","volume":"10","author":"FW Blaisdell","year":"2002","unstructured":"Blaisdell, F. W. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 10, 620\u2013630 (2002).","journal-title":"Cardiovasc Surg"},{"key":"BFsrep16592_CR9","doi-asserted-by":"publisher","first-page":"H1716","DOI":"10.1152\/ajpheart.2001.280.4.H1716","volume":"280","author":"MG Schlag","year":"2001","unstructured":"Schlag, M. G., Harris, K. A. & Potter, R. F. Role of leukocyte accumulation and oxygen radicals in ischemia-reperfusion-induced injury in skeletal muscle. Am J Physiol Heart Circ Physiol 280, H1716\u20131721 (2001).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"BFsrep16592_CR10","doi-asserted-by":"crossref","unstructured":"Lee, D. et al. H2O2-responsive molecularly engineered polymer nanoparticles as ischemia\/reperfusion-targeted nanotherapeutic agents. Sci Rep 3 (2013).","DOI":"10.1038\/srep02233"},{"key":"BFsrep16592_CR11","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1021\/bi9020378","volume":"49","author":"HJ Forman","year":"2010","unstructured":"Forman, H. J., Maiorino, M. & Ursini, F. Signaling Functions of Reactive Oxygen Species. Biochemistry 49, 835\u2013842 (2010).","journal-title":"Biochemistry"},{"key":"BFsrep16592_CR12","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1211\/jpp.59.9.0007","volume":"59","author":"EJ Lim","year":"2007","unstructured":"Lim, E. J., Kang, H. J., Jung, H. J. & Park, E. H. Anti-angiogenic, anti-inflammatory and anti-nociceptive activity of 4-hydroxybenzyl alcohol. J Pharm Pharmacol 59, 1235\u20131240 (2007).","journal-title":"J Pharm Pharmacol"},{"key":"BFsrep16592_CR13","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1016\/j.biomaterials.2010.11.033","volume":"32","author":"S Kim","year":"2011","unstructured":"Kim, S. et al. Reduction of oxidative stress by p-hydroxybenzyl alcohol-containing biodegradable polyoxalate nanoparticulate antioxidant. Biomaterials 32, 3021\u20133029 (2011).","journal-title":"Biomaterials"},{"key":"BFsrep16592_CR14","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1021\/bm100474w","volume":"11","author":"H Park","year":"2010","unstructured":"Park, H. et al. Antioxidant and Anti-Inflammatory Activities of Hydroxybenzyl Alcohol Releasing Biodegradable Polyoxalate Nanoparticles. Biomacromolecules 11, 2103\u20132108 (2010).","journal-title":"Biomacromolecules"},{"key":"BFsrep16592_CR15","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1093\/chromsci\/39.9.393","volume":"39","author":"HX Li","year":"2001","unstructured":"Li, H. X., Ding, M. Y. & Yu, J. Y. Studies on the reaction of p-hydroxybenzyl alcohol and hydroxyl radicals. J Chromatogr Sci 39, 393\u2013396 (2001).","journal-title":"J Chromatogr Sci"},{"key":"BFsrep16592_CR16","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/0028-3908(93)90079-I","volume":"32","author":"JK Liu","year":"1993","unstructured":"Liu, J. K. & Mori, A. Antioxidant and prooxidant activities of P-hydroxybenzyl alcohol and vanilline-Effects on free radicals, brain peroxidation and degradation of benzoate, deoxyribose, amino-acids and DNA. Neuropharmacology 32, 659\u2013669 (1993).","journal-title":"Neuropharmacology"},{"key":"BFsrep16592_CR17","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1248\/bpb.28.1016","volume":"28","author":"SJ Yu","year":"2005","unstructured":"Yu, S. J. et al. Gastrodia elata blume and an active component, p-hydroxybenzyl alcohol reduce focal ischemic brain injury through antioxidant related gene expressions. Biol Pharm Bull 28, 1016\u20131020 (2005).","journal-title":"Biol Pharm Bull"},{"key":"BFsrep16592_CR18","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.intimp.2009.10.009","volume":"10","author":"YW Jang","year":"2010","unstructured":"Jang, Y. W., Lee, J. Y. & Kim, C. J. Anti-asthmatic activity of phenolic compounds from the roots of Gastrodia elata Bl. Int Immunopharmacol 10, 147\u2013154 (2010).","journal-title":"Int Immunopharmacol"},{"key":"BFsrep16592_CR19","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.brainres.2007.08.066","volume":"1181","author":"HJ Kim","year":"2007","unstructured":"Kim, H. J., Hwang, I. K. & Won, M. H. Vanillin, 4-hydroxybenzyl aldehyde and 4-hydroxybenzyl alcohol prevent hippocampal CA1 cell death following global ischemia. Brain Res 1181, 130\u2013141 (2007).","journal-title":"Brain Res"},{"key":"BFsrep16592_CR20","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.brainres.2009.10.037","volume":"1308","author":"SS Yu","year":"2010","unstructured":"Yu, S. S., Zhao, J., Zhen, W. P. & Zhao, Y. Neuroprotective effect of 4-hydroxybenzyl alcohol against transient focal cerebral ischemia via anti-apoptosis in rats. Brain Res 1308, 167\u2013175 (2010).","journal-title":"Brain Res"},{"key":"BFsrep16592_CR21","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.neures.2009.02.005","volume":"64","author":"E Descamps","year":"2009","unstructured":"Descamps, E. et al. Experimental stroke protection induced by 4-hydroxybenzyl alcohol is cancelled by bacitracin. Neurosci Res 64, 137\u2013142 (2009).","journal-title":"Neurosci Res"},{"key":"BFsrep16592_CR22","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.jpba.2008.07.013","volume":"48","author":"LC Lin","year":"2008","unstructured":"Lin, L. C., Chen, Y. F., Lee, W. C., Wu, Y. T. & Tsai, T. H. Pharmacokinetics of gastrodin and its metabolite p-hydroxybenzyl alcohol in rat blood, brain and bile by microdialysis coupled to LC-MS\/MS. J Pharma Biomed Anal 48, 909\u2013917 (2008).","journal-title":"J Pharma Biomed Anal"},{"key":"BFsrep16592_CR23","doi-asserted-by":"publisher","first-page":"6795","DOI":"10.1002\/anie.201003819","volume":"49","author":"JLM Jourden","year":"2010","unstructured":"Jourden, J. L. M. & Cohen, S. M. Hydrogen Peroxide Activated Matrix Metalloproteinase Inhibitors: A Prodrug Approach. Angew Chem Int Ed 49, 6795\u20136797 (2010).","journal-title":"Angew Chem Int Ed"},{"key":"BFsrep16592_CR24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1208\/s12248-008-9009-8","volume":"10","author":"J Rautio","year":"2008","unstructured":"Rautio, J., Laine, K., Gynther, M. & Savolainen, J. Prodrug approaches for CNS delivery. Aaps J 10, 92\u2013102 (2008).","journal-title":"Aaps J"},{"key":"BFsrep16592_CR25","doi-asserted-by":"publisher","first-page":"7968","DOI":"10.1039\/c1cc12526e","volume":"47","author":"JLM Jourden","year":"2011","unstructured":"Jourden, J. L. M., Daniel, K. B. & Cohen, S. M. Investigation of self-immolative linkers in the design of hydrogen peroxide activated metalloprotein inhibitors. Chem Comm 47, 7968\u20137970 (2011).","journal-title":"Chem Comm"},{"key":"BFsrep16592_CR26","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1021\/tx300164j","volume":"25","author":"J Zielonka","year":"2012","unstructured":"Zielonka, J. et al. Boronate Probes as Diagnostic Tools for Real Time Monitoring of Peroxynitrite and Hydroperoxides. Chem Res Toxicol 25, 1793\u20131799 (2012).","journal-title":"Chem Res Toxicol"},{"key":"BFsrep16592_CR27","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1073\/pnas.95.2.675","volume":"95","author":"DC Hooper","year":"1998","unstructured":"Hooper, D. C. et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. ProcNatl Acad Sci USA 95, 675\u2013680 (1998).","journal-title":"ProcNatl Acad Sci USA"},{"key":"BFsrep16592_CR28","doi-asserted-by":"publisher","first-page":"4038","DOI":"10.1002\/adfm.201200773","volume":"22","author":"S Cho","year":"2012","unstructured":"Cho, S. et al. Chemiluminescent and Antioxidant Micelles as Theranostic Agents for Hydrogen Peroxide Associated-Inflammatory Diseases. Advan Funct Mater 22, 4038\u20134043 (2012).","journal-title":"Advan Funct Mater"},{"key":"BFsrep16592_CR29","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0014-5793(97)01197-6","volume":"416","author":"H Possel","year":"1997","unstructured":"Possel, H., Noack, H., Augustin, W., Keilhoff, G. & Wolf, G. 2,7-Dihydrodichlorofluorescein diacetate as a fluorescent marker for peroxynitrite formation. Febs Lett 416, 175\u2013178 (1997).","journal-title":"Febs Lett"},{"key":"BFsrep16592_CR30","first-page":"30","volume":"3","author":"JON Lundberg","year":"1997","unstructured":"Lundberg, J. O. N., Lundberg, J. M., Alving, K. & Weitzberg, E. Nitric oxide and inflammation: The answer is blowing in the wind. NatMed 3, 30\u201331 (1997).","journal-title":"NatMed"},{"key":"BFsrep16592_CR31","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1021\/bm400256h","volume":"14","author":"J Kwon","year":"2013","unstructured":"Kwon, J. et al. Inflammation-Responsive Antioxidant Nanoparticles Based on a Polymeric Prodrug of Vanillin. Biomacromolecules 14, 1618\u20131626 (2013).","journal-title":"Biomacromolecules"},{"key":"BFsrep16592_CR32","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1172\/JCI22493","volume":"115","author":"MR Duranski","year":"2005","unstructured":"Duranski, M. R. et al. Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Inv 115, 1232\u20131240 (2005).","journal-title":"J Clin Inv"},{"key":"BFsrep16592_CR33","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0022-4804(03)00082-9","volume":"111","author":"M Yoshida","year":"2003","unstructured":"Yoshida, M. et al. Intermittent hepatic ischemia-reperfusion minimizes liver metastasis in rats. J Surg Res 111, 255\u2013260 (2003).","journal-title":"J Surg Res"},{"key":"BFsrep16592_CR34","doi-asserted-by":"publisher","first-page":"7661","DOI":"10.4049\/jimmunol.175.11.7661","volume":"175","author":"A Tsung","year":"2005","unstructured":"Tsung, A. et al. Hepatic ischemia\/reperfusion injury involves functional TLR4 signaling in nonparenchymal cells. J Immunol 175, 7661\u20137668 (2005).","journal-title":"J Immunol"},{"key":"BFsrep16592_CR35","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/S0016-5085(03)01209-5","volume":"125","author":"H Jaeschke","year":"2003","unstructured":"Jaeschke, H. & Lemasters, J. J. Apoptosis versus oncotic necrosis in hepatic ischemia\/reperfusion injury. Gastroenterology 125, 1246\u20131257 (2003).","journal-title":"Gastroenterology"},{"key":"BFsrep16592_CR36","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1007\/s10495-013-0814-x","volume":"18","author":"Z Ben-Ari","year":"2013","unstructured":"Ben-Ari, Z. et al. Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia\/reperfusion injury. Apoptosis 18, 547\u2013555 (2013).","journal-title":"Apoptosis"},{"key":"BFsrep16592_CR37","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1097\/00007890-199904270-00003","volume":"67","author":"V Kohli","year":"1999","unstructured":"Kohli, V., Selzner, M., Madden, J. F., Bentley, R. C. & Clavien, P. A. Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation 67, 1099\u20131105 (1999).","journal-title":"Transplantation"},{"key":"BFsrep16592_CR38","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1096\/fj.00-0554fje","volume":"15","author":"D Sindram","year":"2001","unstructured":"Sindram, D., Porte, R. J., Hoffman, M. R., Bentley, R. C. & Clavien, P. A. Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury. Faseb J 15, 1230\u20131232 (2001).","journal-title":"Faseb J"},{"key":"BFsrep16592_CR39","doi-asserted-by":"publisher","first-page":"4631","DOI":"10.1016\/j.polymer.2011.07.057","volume":"52","author":"JN Cambre","year":"2011","unstructured":"Cambre, J. N. & Sumerlin, B. S. Biomedical applications of boronic acid polymers. Polymer 52, 4631\u20134643 (2011).","journal-title":"Polymer"},{"key":"BFsrep16592_CR40","doi-asserted-by":"publisher","first-page":"15392","DOI":"10.1021\/ja0441716","volume":"126","author":"MCY Chang","year":"2004","unstructured":"Chang, M. C. Y., Pralle, A., Isacoff, E. Y. & Chang, C. J. A selective, cell-permeable optical probe for hydrogen peroxide in living cells. J Am Chem Soc 126, 15392\u201315393 (2004).","journal-title":"J Am Chem Soc"},{"key":"BFsrep16592_CR41","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1021\/ar200126t","volume":"44","author":"AR Lippert","year":"2011","unstructured":"Lippert, A. R., De Bittner, G. C. V. & Chang, C. J. Boronate Oxidation as a Bioorthogonal Reaction Approach for Studying the Chemistry of Hydrogen Peroxide in Living Systems. Acc Chem Res 44, 793\u2013804 (2011).","journal-title":"Acc Chem Res"},{"key":"BFsrep16592_CR42","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1152\/physrev.00029.2006","volume":"87","author":"P Pacher","year":"2007","unstructured":"Pacher, P., Beckman, J. S. & Liaudet, L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87, 315\u2013424 (2007).","journal-title":"Physiol Rev"},{"key":"BFsrep16592_CR43","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.bbagen.2013.05.004","volume":"1840","author":"CC Winterbourn","year":"2014","unstructured":"Winterbourn, C. C. The challenges of using fluorescent probes to detect and quantify specific reactive oxygen species in living cells. Biochim Biophy Acta 1840, 730\u2013738 (2014).","journal-title":"Biochim Biophy Acta"},{"key":"BFsrep16592_CR44","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1021\/cb800279q","volume":"4","author":"G Ferrer-Sueta","year":"2009","unstructured":"Ferrer-Sueta, G. & Radi, R. Chemical Biology of Peroxynitrite: Kinetics, Diffusion and Radicals. Acs Chem Biol 4, 161\u2013177 (2009).","journal-title":"Acs Chem Biol"},{"key":"BFsrep16592_CR45","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/physrev.00018.2001","volume":"82","author":"W Droge","year":"2002","unstructured":"Droge, W. Free radicals in the physiological control of cell function. Physiol Rev 82, 47\u201395 (2002).","journal-title":"Physiol Rev"},{"key":"BFsrep16592_CR46","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jss.2003.04.001","volume":"116","author":"TM Woodruff","year":"2004","unstructured":"Woodruff, T. M. et al. Protective effects of a potent C5a receptor antagonist on experimental acute limb ischemia-reperfusion in rats. J Surg Res 116, 81\u201390 (2004).","journal-title":"J Surg Res"},{"key":"BFsrep16592_CR47","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1001\/archinte.167.15.1610","volume":"167","author":"NR Cook","year":"2007","unstructured":"Cook, N. R. et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women\u2019s Antioxidant Cardiovascular Study. Arch Intern Med 167, 1610\u20131618 (2007).","journal-title":"Arch Intern Med"},{"key":"BFsrep16592_CR48","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1016\/S0140-6736(03)13637-9","volume":"361","author":"DP Vivekananthan","year":"2003","unstructured":"Vivekananthan, D. P., Penn, M. S., Sapp, S. K., Hsu, A. & Topol, E. J. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361, 2017\u20132023 (2003).","journal-title":"Lancet"},{"key":"BFsrep16592_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molcel.2007.03.016","volume":"26","author":"EA Veal","year":"2007","unstructured":"Veal, E. A., Day, A. M. & Morgan, B. A. Hydrogen peroxide sensing and signaling. Mol Cell 26, 1\u201314 (2007).","journal-title":"Mol Cell"},{"key":"BFsrep16592_CR50","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1002\/adma.201200420","volume":"24","author":"YL Colson","year":"2012","unstructured":"Colson, Y. L. & Grinstaff, M. W. Biologically responsive polymeric nanoparticles for drug delivery. Adv Mater 24, 3878\u20133886 (2012).","journal-title":"Adv Mater"},{"key":"BFsrep16592_CR51","doi-asserted-by":"publisher","first-page":"M379","DOI":"10.1111\/j.1750-3841.2009.01287.x","volume":"74","author":"RS Pei","year":"2009","unstructured":"Pei, R. S., Zhou, F., Ji, B. P. & Xu, J. Evaluation of combined antibacterial effects of eugenol, cinnamaldehyde, thymol and carvacrol against E. coli with an improved method. J Food Sci 74, M379\u2013383 (2009).","journal-title":"J Food Sci"},{"key":"BFsrep16592_CR52","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1211\/jpp.59.9.0007","volume":"59","author":"EJ Lim","year":"2007","unstructured":"Lim, E. J., Kang, H. J., Jung, H. J. & Park, E. H. Anti-angiogenic, anti-inflammatory and anti-nociceptive activity of 4-hydroxybenzyl alcohol. J Pharm Pharmacol 59, 1235\u20131240 (2007).","journal-title":"J Pharm Pharmacol"},{"key":"BFsrep16592_CR53","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00395-011-0164-1","volume":"106","author":"S Choudhury","year":"2011","unstructured":"Choudhury, S. et al. Mitochondria to nucleus translocation of AIF in mice lacking Hsp70 during ischemia\/reperfusion. Basic Res Cardiol 106, 397\u2013407 (2011).","journal-title":"Basic Res Cardiol"},{"key":"BFsrep16592_CR54","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1038\/srep02233","volume":"3","author":"D Lee","year":"2013","unstructured":"Lee, D. et al. H2O2-responsive molecularly engineered polymer nanoparticles as ischemia\/reperfusion-targeted nanotherapeutic agents. Sci Rep 3, 2233 (2013).","journal-title":"Sci Rep"},{"key":"BFsrep16592_CR55","doi-asserted-by":"publisher","first-page":"H1374","DOI":"10.1152\/ajpheart.00168.2010","volume":"299","author":"S Bae","year":"2010","unstructured":"Bae, S. et al. Delayed activation of caspase-independent apoptosis during heart failure in transgenic mice overexpressing caspase inhibitor CrmA. Am J Physiol Heart Circ Physiol 299, H1374\u20131381 (2010).","journal-title":"Am J Physiol Heart Circ Physiol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep16592.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep16592","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep16592.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T08:12:05Z","timestamp":1672906325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep16592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,13]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,21]]}},"alternative-id":["BFsrep16592"],"URL":"https:\/\/doi.org\/10.1038\/srep16592","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,13]]},"assertion":[{"value":"1 April 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16592"}}