{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:07:40Z","timestamp":1780567660593,"version":"3.54.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100021077","name":"Vice Chancellor for Research and Technology, Kerman University of Medical Sciences","doi-asserted-by":"publisher","award":["403000869"],"award-info":[{"award-number":["403000869"]}],"id":[{"id":"10.13039\/501100021077","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Appl Physiol"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s00421-025-06086-5","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:29:35Z","timestamp":1766122175000},"page":"2695-2705","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of ischemic postconditioning on inflammatory and oxidative markers in methadone-treated rats during myocardial ischemia-reperfusion injury"],"prefix":"10.1007","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8758-6686","authenticated-orcid":false,"given":"Beydolah","family":"Shahouzehi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6196-0775","authenticated-orcid":false,"given":"Hossein","family":"Fallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-5568","authenticated-orcid":false,"given":"Mahboobeh","family":"Yeganeh-Hajahmadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"6086_CR1","first-page":"577","volume":"14","author":"S Alinejad","year":"2015","unstructured":"Alinejad S, Kazemi T, Zamani N et al (2015) A systematic review of the cardiotoxicity of methadone. EXCLI J 14:577","journal-title":"EXCLI J"},{"key":"6086_CR2","doi-asserted-by":"publisher","first-page":"e42179","DOI":"10.1371\/journal.pone.0042179","volume":"7","author":"D Brevoord","year":"2012","unstructured":"Brevoord D, Kranke P, Kuijpers M et al (2012) Remote ischemic conditioning to protect against ischemia-reperfusion injury: a systematic review and meta-analysis. PLoS One 7:e42179. https:\/\/doi.org\/10.1371\/journal.pone.0042179","journal-title":"PLoS One"},{"key":"6086_CR3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.freeradbiomed.2014.06.021","volume":"74","author":"M Buelna-Chontal","year":"2014","unstructured":"Buelna-Chontal M, Guevara-Ch\u00e1vez J-G, Silva-Palacios A et al (2014) Nrf2-regulated antioxidant response is activated by protein kinase C in postconditioned rat hearts. Free Radic Biol Med 74:145\u2013156","journal-title":"Free Radic Biol Med"},{"key":"6086_CR4","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3892\/etm.2015.2514","volume":"10","author":"HUI Chen","year":"2015","unstructured":"Chen HUI, Wang LEI, Xing B-Z et al (2015) Ischemic postconditioning attenuates inflammation in rats following renal ischemia and reperfusion injury. Exp Ther Med 10:513\u2013518. https:\/\/doi.org\/10.3892\/etm.2015.2514","journal-title":"Exp Ther Med"},{"key":"6086_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/6954764","volume":"2020","author":"R Chen","year":"2020","unstructured":"Chen R, Zhang Y, Lan J et al (2020) Ischemic postconditioning alleviates intestinal ischemia-reperfusion injury by enhancing autophagy and suppressing oxidative stress through the Akt\/GSK-3\u03b2\/Nrf2 pathway in mice. Oxid Med Cell Longev 2020:1\u201314. https:\/\/doi.org\/10.1155\/2020\/6954764","journal-title":"Oxid Med Cell Longev"},{"key":"6086_CR6","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.3390\/life15071084","volume":"15","author":"BG Cristina","year":"2025","unstructured":"Cristina BG, Isac S, Teodorescu G-D et al (2025) Methadone-induced toxicity\u2014an unexpected challenge for the brain and heart in ICU settings: case report and review of the literature. Life 15:1084. https:\/\/doi.org\/10.3390\/life15071084","journal-title":"Life"},{"key":"6086_CR7","unstructured":"Doring HJ, Dehnert H (1987) The isolated perfused heart according to Langendorff. BVM-Biomesstechnik"},{"key":"6086_CR8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.4103\/jrpp.jrpp_49_24","volume":"13","author":"G Dorooshi","year":"2024","unstructured":"Dorooshi G, Shirmohammadi M, Gheshlaghi F et al (2024) Cardiovascular complications following acute methadone poisoning in patients with and without a history of long-term methadone use. J Res Pharm Pract 13:58\u201364. https:\/\/doi.org\/10.4103\/jrpp.jrpp_49_24","journal-title":"J Res Pharm Pract"},{"key":"6086_CR9","doi-asserted-by":"publisher","first-page":"e001307","DOI":"10.1136\/openhrt-2020-001307","volume":"7","author":"H Fernando","year":"2020","unstructured":"Fernando H, Nehme Z, Peter K et al (2020) Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction. Open Heart 7:e001307. https:\/\/doi.org\/10.1136\/openhrt-2020-001307","journal-title":"Open Heart"},{"key":"6086_CR10","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1213\/ANE.0b013e3181b92201","volume":"109","author":"ER Gross","year":"2009","unstructured":"Gross ER, Hsu AK, Gross GJ (2009) Acute methadone treatment reduces myocardial infarct size via the \u03b4-opioid receptor in rats during reperfusion. Anesth Analg 109:1395\u20131402","journal-title":"Anesth Analg"},{"key":"6086_CR11","doi-asserted-by":"publisher","first-page":"H2201","DOI":"10.1152\/ajpheart.00815.2009","volume":"298","author":"GJ Gross","year":"2010","unstructured":"Gross GJ, Baker JE, Hsu A et al (2010) Evidence for a role of opioids in epoxyeicosatrienoic acid-induced cardioprotection in rat hearts. Am J Physiol Heart Circ Physiol 298:H2201\u2013H2207","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"6086_CR12","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.5152\/eurasianjmed.2022.22293","volume":"54","author":"MC G\u00fcler","year":"2022","unstructured":"G\u00fcler MC, Tanyeli A, Akdemir FNE et al (2022) An overview of ischemia\u2013reperfusion injury: review on oxidative stress and inflammatory response. Eurasian J Med 54:S62","journal-title":"Eurasian J Med"},{"key":"6086_CR13","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1111\/bph.13042","volume":"172","author":"JP Headrick","year":"2015","unstructured":"Headrick JP, See Hoe LE, Du Toit EF, Peart JN (2015) Opioid receptors and cardioprotection \u2013 \u2018opioidergic conditioning\u2019 of the heart. Br J Pharmacol 172:2026\u20132050. https:\/\/doi.org\/10.1111\/bph.13042","journal-title":"Br J Pharmacol"},{"key":"6086_CR14","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-019-0756-8","author":"G Heusch","year":"2019","unstructured":"Heusch G (2019) Coronary microvascular obstruction: the new frontier in cardioprotection. Basic Res Cardiol. https:\/\/doi.org\/10.1007\/s00395-019-0756-8","journal-title":"Basic Res Cardiol"},{"key":"6086_CR15","unstructured":"Iranian Ministry of Health (2020) Methadone usage reports. Tehran"},{"key":"6086_CR16","doi-asserted-by":"publisher","first-page":"H1","DOI":"10.1152\/ajpheart.00145.2018","volume":"316","author":"A Jamaiyar","year":"2019","unstructured":"Jamaiyar A, Juguilon C, Dong F et al (2019) Cardioprotection during ischemia by coronary collateral growth. Am J Physiol Heart Circ Physiol 316:H1\u2013H9. https:\/\/doi.org\/10.1152\/ajpheart.00145.2018","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"6086_CR17","doi-asserted-by":"publisher","first-page":"773","DOI":"10.2147\/tcrm.s195267","volume":"15","author":"M Jannati","year":"2019","unstructured":"Jannati M, Attar A (2019) Analgesia and sedation post-coronary artery bypass graft surgery: a review of the literature. Ther Clin Risk Manag 15:773\u2013781. https:\/\/doi.org\/10.2147\/tcrm.s195267","journal-title":"Ther Clin Risk Manag"},{"key":"6086_CR18","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1111\/anae.12974","volume":"70","author":"N Jivraj","year":"2015","unstructured":"Jivraj N, Liew F, Marber M (2015) Ischaemic postconditioning: cardiac protection after the event. Anaesthesia 70:598\u2013612. https:\/\/doi.org\/10.1111\/anae.12974","journal-title":"Anaesthesia"},{"key":"6086_CR19","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3390\/biomedicines10030574","volume":"10","author":"A Jurcau","year":"2022","unstructured":"Jurcau A, Ardelean AI (2022) Oxidative stress in ischemia\/reperfusion injuries following acute ischemic stroke. Biomedicines 10:574. https:\/\/doi.org\/10.3390\/biomedicines10030574","journal-title":"Biomedicines"},{"key":"6086_CR20","doi-asserted-by":"publisher","first-page":"3710","DOI":"10.1111\/bph.70097","volume":"182","author":"V Katari","year":"2025","unstructured":"Katari V, Dalal KK, Kondapalli N et al (2025) Opioid receptors in cardiovascular function. Br J Pharmacol 182:3710\u20133725. https:\/\/doi.org\/10.1111\/bph.70097","journal-title":"Br J Pharmacol"},{"key":"6086_CR21","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ijcard.2010.08.010","volume":"146","author":"S Lavi","year":"2011","unstructured":"Lavi S, Lavi R (2011) Conditioning of the heart: from pharmacological interventions to local and remote protection. Int J Cardiol 146:311\u2013318. https:\/\/doi.org\/10.1016\/j.ijcard.2010.08.010","journal-title":"Int J Cardiol"},{"key":"6086_CR22","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S0014-2999(99)00322-2","volume":"374","author":"J-G Liu","year":"1999","unstructured":"Liu J-G, Liao X-P, Gong Z-H, Qin B-Y (1999) Methadone-induced desensitization of the \u03b4-opioid receptor is mediated by uncoupling of receptor from G protein. Eur J Pharmacol 374:301\u2013308","journal-title":"Eur J Pharmacol"},{"key":"6086_CR23","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.2478\/s11756-020-00432-y","volume":"75","author":"Y Masoumi-Ardakani","year":"2020","unstructured":"Masoumi-Ardakani Y, Aminizadeh S, Fallah H, Shahouzehi B (2020) L-Carnitine different doses affect serum and pancreas tissue antioxidative defense and histopathology in STZ-induced diabetic rats. Biol (Bratisl) 75:1415\u20131423. https:\/\/doi.org\/10.2478\/s11756-020-00432-y","journal-title":"Biol (Bratisl)"},{"key":"6086_CR24","first-page":"257","volume":"13","author":"A Mohammadi","year":"2017","unstructured":"Mohammadi A, Fallah H, Shahouzehi B, Najafipour H (2017) miR-33 inhibition attenuates the effect of liver X receptor agonist T0901317 on expression of liver X receptor alpha in mice liver. ARYA Atheroscler 13:257","journal-title":"ARYA Atheroscler"},{"key":"6086_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177824","author":"AV Mukhomedzyanov","year":"2025","unstructured":"Mukhomedzyanov AV, Maslov LN, Popov SV, Naryzhnaya NV (2025) Could peptide opioid receptor agonists become drugs for treatment of acute myocardial infarction? Eur J Pharmacol. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177824","journal-title":"Eur J Pharmacol"},{"key":"6086_CR26","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.3390\/biomedicines11071887","volume":"11","author":"NV Naryzhnaya","year":"2023","unstructured":"Naryzhnaya NV, Mukhomedzyanov AV, Sirotina M et al (2023) \u03b4-opioid receptor as a molecular target for increasing cardiac resistance to reperfusion in drug development. Biomedicines 11:1887","journal-title":"Biomedicines"},{"key":"6086_CR27","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.brainresbull.2021.03.009","volume":"171","author":"E Nylander","year":"2021","unstructured":"Nylander E, Zelleroth S, Nyberg F et al (2021) The effects of morphine, methadone, and fentanyl on mitochondria: a live cell imaging study. Brain Res Bull 171:126\u2013134","journal-title":"Brain Res Bull"},{"key":"6086_CR28","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1007\/s11481-011-9292-5","volume":"6","author":"S Roy","year":"2011","unstructured":"Roy S, Ninkovic J, Banerjee S et al (2011) Opioid drug abuse and modulation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol 6:442\u2013465. https:\/\/doi.org\/10.1007\/s11481-011-9292-5","journal-title":"J Neuroimmune Pharmacol"},{"key":"6086_CR29","first-page":"46","volume":"13","author":"A Salarian","year":"2018","unstructured":"Salarian A, Kadkhodaee M, Zahmatkesh M et al (2018) Opioid use disorder induces oxidative stress and inflammation: the attenuating effect of methadone maintenance treatment. Iran J Psychiatry 13:46","journal-title":"Iran J Psychiatry"},{"key":"6086_CR30","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaf500","author":"J Schofield","year":"2025","unstructured":"Schofield J, Conti AA, Khan F, Baldacchino AM (2025) Association between chronic opioid exposure and cardiovascular disease: a systematic review and meta-analysis. Eur J Prev Cardiol. https:\/\/doi.org\/10.1093\/eurjpc\/zwaf500","journal-title":"Eur J Prev Cardiol"},{"key":"6086_CR31","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1177\/1535370216684041","volume":"242","author":"M Seewald","year":"2016","unstructured":"Seewald M, Coles JA, Sigg DC, Iaizzo PA (2016) Featured article: pharmacological postconditioning with delta opioid attenuates myocardial reperfusion injury in isolated porcine hearts. Exp Biol Med 242:986\u2013995. https:\/\/doi.org\/10.1177\/1535370216684041","journal-title":"Exp Biol Med"},{"key":"6086_CR32","doi-asserted-by":"publisher","DOI":"10.15407\/ubj90.01.034","volume":"90","author":"B Shahouzehi","year":"2018","unstructured":"Shahouzehi B, Shabani M, Shahrokhi N et al (2018) Effects of Pistacia atlantica resin oil on the level of VEGF, hydroxyproline, antioxidant and wound healing activity in STZ-induced diabetic rats. Ukrainian Biochem J 90:34\u201341. https:\/\/doi.org\/10.15407\/ubj90.01.034","journal-title":"Ukrainian Biochem J"},{"key":"6086_CR33","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.121.021260","author":"JH Singleton","year":"2021","unstructured":"Singleton JH, Abner EL, Akpunonu PD, Kucharska-Newton AM (2021) Association of nonacute opioid use and cardiovascular diseases: a scoping review of the literature. J Am Heart Assoc. https:\/\/doi.org\/10.1161\/jaha.121.021260","journal-title":"J Am Heart Assoc"},{"key":"6086_CR34","first-page":"104","volume":"3","author":"K Soltaninejad","year":"2014","unstructured":"Soltaninejad K, Hassanian-Moghaddam H, Shadnia S (2014) Methadone related poisoning on the rise in Tehran, Iran. Asia Pac J Med Toxicol 3:104\u2013109","journal-title":"Asia Pac J Med Toxicol"},{"key":"6086_CR35","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1007\/s00395-011-0210-z","volume":"106","author":"S Tamareille","year":"2011","unstructured":"Tamareille S, Mateus V, Ghaboura N et al (2011) Risk and SAFE signaling pathway interactions in remote limb ischemic perconditioning in combination with local ischemic postconditioning. Basic Res Cardiol 106:1329\u20131339. https:\/\/doi.org\/10.1007\/s00395-011-0210-z","journal-title":"Basic Res Cardiol"},{"key":"6086_CR36","doi-asserted-by":"publisher","first-page":"5696","DOI":"10.2174\/1381612820666140204120311","volume":"20","author":"K Tanaka","year":"2014","unstructured":"Tanaka K, Kersten J, Riess M (2014) Opioid-induced cardioprotection. Curr Pharm Des 20:5696\u20135705. https:\/\/doi.org\/10.2174\/1381612820666140204120311","journal-title":"Curr Pharm Des"},{"key":"6086_CR37","unstructured":"World Drug Report (2021) (2021) United Nations office on Drug and Crime"},{"key":"6086_CR38","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s10557-010-6236-x","volume":"24","author":"X Yang","year":"2010","unstructured":"Yang X, Cohen MV, Downey JM (2010) Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc Drugs Ther 24:225\u2013234. https:\/\/doi.org\/10.1007\/s10557-010-6236-x","journal-title":"Cardiovasc Drugs Ther"},{"key":"6086_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-65349-x","author":"M Yeganeh-Hajahmadi","year":"2024","unstructured":"Yeganeh-Hajahmadi M, Kordestani Z, Moosavi-Saeed Y, Rostamzadeh F (2024) Inhibition of the protective effects of preconditioning in ischemia\u2013reperfusion injury by chronic methadone: the role of pAkt and pSTAT3. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-024-65349-x","journal-title":"Sci Rep"},{"key":"6086_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2008.05.567","volume":"17","author":"A Zatta","year":"2008","unstructured":"Zatta A, Kin H, Yoshishige D et al (2008) Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. Heart Lung Circ 17:S226. https:\/\/doi.org\/10.1016\/j.hlc.2008.05.567","journal-title":"Heart Lung Circ"},{"key":"6086_CR41","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s11010-012-1458-9","volume":"372","author":"X Zhang","year":"2013","unstructured":"Zhang X, Xiao Z, Yao J et al (2013) Participation of protein kinase C in the activation of Nrf2 signaling by ischemic preconditioning in the isolated rabbit heart. Mol Cell Biochem 372:169\u2013179","journal-title":"Mol Cell Biochem"}],"container-title":["European Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00421-025-06086-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00421-025-06086-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00421-025-06086-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:48:17Z","timestamp":1780566497000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00421-025-06086-5"}},"subtitle":["Cardioprotective effects of IPoC in methadone exposure"],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["6086"],"URL":"https:\/\/doi.org\/10.1007\/s00421-025-06086-5","relation":{},"ISSN":["1439-6319","1439-6327"],"issn-type":[{"value":"1439-6319","type":"print"},{"value":"1439-6327","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]},"assertion":[{"value":"13 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The experimental protocol was approved by Animal Care Committee of the Ethics Committee of Kerman University of Medical Sciences (IR.KMU.AEC.1403.101). All methods were performed in accordance with guidelines and regulations of the Ethics Committee of Kerman University of Medical Sciences and the ARRIVE (Animal Research: Reporting of in Vivo Experiments, guidelines 2.0).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}