ARNI co-treatment significantly lowered GRP78 staining intensity and reduced degenerative changes in cardiomyocytes compared to DOX alone in a rat model of doxorubicin-induced cardiomyopathy.
Does ARNI mitigate ER stress and myocardial injury in a doxorubicin-induced cardiomyopathy rat model?
ARNI co-treatment mitigates endoplasmic reticulum stress and myocardial injury in a rat model of doxorubicin-induced cardiomyopathy, suggesting potential cardioprotective benefits during anthracycline chemotherapy.
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.
Unvan et al. (Thu,) conducted a other in Doxorubicin-induced cardiomyopathy. ARNI (LCZ696) vs. Control, DOX alone was evaluated on GRP78 protein expression and cardiomyocyte degenerative changes. ARNI co-treatment significantly lowered GRP78 staining intensity and reduced degenerative changes in cardiomyocytes compared to DOX alone in a rat model of doxorubicin-induced cardiomyopathy.