{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:27:43Z","timestamp":1787138863523,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["CRG\/2021\/000227"],"award-info":[{"award-number":["CRG\/2021\/000227"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["3\/1\/2(22)\/Env\/2021\u2010NCD\u2010II"],"award-info":[{"award-number":["3\/1\/2(22)\/Env\/2021\u2010NCD\u2010II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fine particulate matter (PM\n                    <jats:sub>2.5<\/jats:sub>\n                    ) is a recognized cardiovascular toxicant, yet the exposure duration at which mitochondrial stress responses transition from adaptive to persistently injurious remains poorly defined. Here, we identified a duration\u2010dependent transition in mitochondrial responses under the present exposure conditions. Female Wistar rats were exposed to PM\n                    <jats:sub>2.5<\/jats:sub>\n                    (250\u2009\u03bcg\/m\n                    <jats:sup>3<\/jats:sup>\n                    , 3\u2009h\/day) for 1, 7, 14, or 21\u2009days, followed by integrated evaluation of cardiac mitochondrial bioenergetics, redox balance, quality control pathways, and ex\u00a0vivo cardiac function, with washout validation. Short\u2010term exposure (1\u20137\u2009days) elicited transient mitochondrial oxidative stress and activation of adaptive quality control responses without impairing respiratory efficiency, electron transport chain activity, ATP production, or cardiac performance; these changes returned to values comparable to controls after a 24\u2010h pollutant\u2010free washout under the present experimental conditions. Under the exposure conditions employed, sustained mitochondrial dysfunction first became evident after 14\u2009days of repeated exposure, characterized by coordinated suppression of mitochondrial respiration, ETC complex activities, and ATP synthesis, accompanied by mitochondrial DNA depletion, impaired biogenesis and quality control signaling, sustained oxidative stress, and intramitochondrial metal accumulation. Notably, mitochondrial and cardiac functional deficits induced after \u2265\u200914\u2009days persisted despite washout, indicating that these deficits were not restored within the 24\u2010h recovery period examined, rather than reflecting delayed recovery within this window. Collectively, these findings define a duration\u2010dependent temporal toxicity progression at which repeated PM\n                    <jats:sub>2.5<\/jats:sub>\n                    exposure shifts cardiac mitochondria from transient, recoverable stress responses to persistent bioenergetic impairment under the present experimental conditions providing a mechanistic basis for exposure\u2010duration\u2013informed cardiovascular hazard characterization.\n                  <\/jats:p>","DOI":"10.1002\/tox.70189","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:03:53Z","timestamp":1787137433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Repeated\n                    <scp>\n                      PM\n                      <sub>2<\/sub>\n                    <\/scp>\n                    <sub>.5<\/sub>\n                    Inhalation Exposure Drives a Duration\u2010Dependent Transition From Mitochondrial Adaptation to Persistent Cardiac Toxicity in Rats"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-8150","authenticated-orcid":false,"given":"Bhavana","family":"Sivakumar","sequence":"first","affiliation":[{"name":"Department of Radiology and Imaging Sciences Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2051-2399","authenticated-orcid":false,"given":"Gino A.","family":"Kurian","sequence":"additional","affiliation":[{"name":"School of Chemical and Biotechnology, SASTRA Deemed University  Thanjavur Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwag005"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.25122\/jml\u20102025\u20100018"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.5487\/TR.2014.30.2.071"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.0561"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366\u20106999.212942"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.110483"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012\u2010022\u201009737\u20107"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2023.153466"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/envhealth.3c00168"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109769"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13182"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1515\/reveh\u20102020\u20100127"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S340301"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6123"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103158"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083784"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2024.12756"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.119236"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2021.09.010"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.10.009"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.265819"}],"container-title":["Environmental 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