{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:22:49Z","timestamp":1777886569476,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>One of the most serious complications associated with the use of the chemotherapeutic agent doxorubicin (DOX) is cardiomyopathy. Although cardioprotective drugs such as angiotensin receptor\u2010neprilysin inhibitors (ARNI) are used to prevent cardiomyopathy in DOX patients, no studies have reported the relationship between ARNI and endoplasmic reticulum (ER) stress in DOX\u2010mediated cardiomyopathy. The aim of the present study was to investigate the possible changes in the GRP78 protein associated with ER stress in the heart failure model developed by DOX\u2010induced cardiomyopathy in rats and to evaluate whether ARNI (LCZ696) given for treatment is effective on this protein. Male Wistar albino rats were divided into five groups: control, DOX, ARNI, DOX\u2009+\u2009ARNI, and post\u2010DOX\/ARNI. Body weights were monitored. Heart tissue sections were stained with hematoxylin\u2013eosin. GRP78 expression was assessed with immunohistochemical labelling. The body weights of the rats in the DOX and post\u2010DOX\/ARNI groups were significantly reduced compared with the control and ARNI groups. Less degenerative changes were revealed in cardiomyocytes in the DOX\u2009+\u2009ARNI group compared with the cardiomyocytes in both the DOX and post\u2010DOX\/ARNI groups. When comparing the intensity of GRP78 staining, the intensity was significantly lower in the control, ARNI, and DOX\u2009+\u2009ARNI groups than in the DOX and post\u2010DOX\/ARNI groups. These results suggest that ARNI co\u2010treatment mitigates ER stress and myocardial injury in DOX\u2010induced cardiomyopathy. Therefore, ARNI may provide dual benefits in terms of both symptom management and cardioprotection during anthracycline chemotherapy.<\/jats:p>","DOI":"10.1002\/jat.70212","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T03:42:40Z","timestamp":1777606960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of Angiotensin Receptor Neprilysin Inhibitor on Endoplasmic Reticulum Stress in Doxorubicin\u2010Mediated Cardiomyopathy\u2010Associated Heart Failure Model in Rats"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-1963","authenticated-orcid":false,"given":"Mert","family":"Unvan","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Mersin University  Mersin Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-2640","authenticated-orcid":false,"given":"Meryem \u0130lkay","family":"Karag\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Hatay Mustafa Kemal University  Antakya Hatay Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1086-713X","authenticated-orcid":false,"given":"Hatice Oru\u00e7","family":"Demirba\u011f","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Mersin University  Mersin Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9950-5548","authenticated-orcid":false,"given":"Ebru","family":"Balli","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Mersin University  Mersin Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557\u2010020\u201007099\u20102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951119002622"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22842"},{"issue":"12","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/antiox10121897","article-title":"Endoplasmic Reticulum Stress Promotes iNOS\/NO and Influences Inflammation in the Development of Doxorubicin\u2010Induced Cardiomyopathy","volume":"10","author":"Bagchi A. 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