The Effects of Angiotensin Receptor Neprilysin Inhibitor on Endoplasmic Reticulum Stress in Doxorubicin-Mediated Cardiomyopathy-Associated Heart Failure Model in Rats
Journal of Applied Toxicology, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/jat.70212
- Dergi Adı: Journal of Applied Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Chemical Abstracts Core, Chimica, EMBASE, Environment Index, MEDLINE, Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: angiotensin receptor-neprilysin inhibitor, cardiomyopathy, doxorubicin, endoplasmic reticulum stress, GRP78
- Hatay Mustafa Kemal Üniversitesi Adresli: Evet
Özet
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-neprilysin 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-mediated 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-induced 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 + ARNI, and post-DOX/ARNI. Body weights were monitored. Heart tissue sections were stained with hematoxylin–eosin. GRP78 expression was assessed with immunohistochemical labelling. The body weights of the rats in the DOX and post-DOX/ARNI groups were significantly reduced compared with the control and ARNI groups. Less degenerative changes were revealed in cardiomyocytes in the DOX + ARNI group compared with the cardiomyocytes in both the DOX and post-DOX/ARNI groups. When comparing the intensity of GRP78 staining, the intensity was significantly lower in the control, ARNI, and DOX + ARNI groups than in the DOX and post-DOX/ARNI groups. These results suggest that ARNI co-treatment mitigates ER stress and myocardial injury in DOX-induced cardiomyopathy. Therefore, ARNI may provide dual benefits in terms of both symptom management and cardioprotection during anthracycline chemotherapy.