.webp&w=384&q=75){kind=logo}
Loading, please wait...
Loading, please wait...
Managing doxorubicin-induced cardiotoxicity remains a significant challenge for clinicians treating various cancers. Doxorubicin (DOX) effectively kills cancer cells but often triggers severe cardiomyopathy, leading to heart failure. Consequently, researchers continue to explore various protective strategies. Recent experimental data highlights the potential role of ARNI in doxorubicin cardiomyopathy, specifically through its impact on endoplasmic reticulum (ER) stress pathways.
Endoplasmic reticulum stress occurs when misfolded proteins accumulate within cells. The 78-kDa glucose-regulated protein (GRP78) serves as a critical marker for this process. Specifically, high levels of GRP78 indicate significant cellular stress. When doxorubicin triggers oxidative stress in cardiomyocytes, it disrupts the protein-folding environment. This disruption leads to ER stress and subsequent heart tissue damage. However, emerging evidence suggests that Angiotensin Receptor Neprilysin Inhibitors (ARNI), like LCZ696, may counteract this pathway.
In a recent experimental study, researchers utilized male Wistar albino rats to test the efficacy of ARNI against DOX-induced injury. They divided the rats into five groups: a control group, a DOX-only group, an ARNI-only group, a co-treatment (DOX + ARNI) group, and a post-treatment (post-DOX/ARNI) group. The researchers monitored body weights and performed detailed histological analysis on heart tissue sections.
The results were telling. Rats in the DOX and post-DOX/ARNI groups experienced significant weight loss compared to the control and ARNI groups. Furthermore, histological staining revealed that the co-treatment (DOX + ARNI) group had significantly fewer degenerative changes in cardiomyocytes compared to the DOX-only group. Notably, the intensity of GRP78 staining—the marker for ER stress—was significantly lower in the ARNI co-treatment group. This finding suggests that ARNI effectively protects heart cells from the toxic effects of DOX by mitigating cellular stress responses.
These results indicate that ARNI may offer dual benefits during anthracycline chemotherapy. Beyond managing symptoms of heart failure, ARNI appears to provide active cardioprotection by preventing the onset of myocardial injury. Therefore, clinicians might consider ARNI as a viable strategy to preserve cardiac health in patients undergoing chemotherapy with cardiotoxic agents.
ARNI works by reducing endoplasmic reticulum (ER) stress markers like GRP78 and minimizing degenerative changes in cardiomyocytes, thereby preventing the structural damage typically caused by doxorubicin.
While doxorubicin often leads to significant weight loss in experimental models, the study suggests that ARNI co-treatment primarily focuses on protecting heart tissue and mitigating internal cellular stress rather than fully reversing systemic weight changes.
GRP78 is a molecular chaperone that increases when the endoplasmic reticulum is under stress. Measuring its expression helps researchers determine if a drug is successfully protecting heart cells from toxic damage.
Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. Always seek the advice of a physician or other qualified health provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.
References
Unvan M et al. The Effects of Angiotensin Receptor Neprilysin Inhibitor on Endoplasmic Reticulum Stress in Doxorubicin-Mediated Cardiomyopathy-Associated Heart Failure Model in Rats. J Appl Toxicol. 2026 Apr 30. doi: 10.1002/jat.70212. PMID: 42062800.
Kim S, et al. Sacubitril/valsartan reduces endoplasmic reticulum stress in a rat model of doxorubicin-induced cardiotoxicity. Life Sci. 2022 Feb 15;291:120275. doi: 10.1016/j.lfs.2021.120275. PMID: 34973278.
El-Gohary OA, et al. Potential role of endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity-an update. Front Pharmacol. 2024 Aug 12;15:1434938. doi: 10.3389/fphar.2024.1434938. PMID: 39192994.
"
Read summarized clinical updates, watch expert medical content, and earn CME certifications right from your smartphone.
Open your smartphone camera to scan and install.
A new study reveals that ARNI (LCZ696) reduces GRP78 protein expression, mitigating ER stress and heart damage caused by doxorubicin chemotherapy in rat mod...
2 months ago
Andhra Pradesh reported 10 new Covid-19 cases, taking the state tally to 49 while deaths remain at four. With 24 patients hospitalized and 16 under home isolation, the Health Department has intensified monitoring. Medical professionals should review regional distribution, diagnostic protocols, and management plans.
Today
An 11-year Swedish registry study of 618 uterine sarcoma patients found that minimally invasive surgery yielded survival comparable to open surgery in early stages. However, adjuvant chemotherapy conferred no survival benefit in localized or advanced disease, highlighting stage and histology as key outcomes.
3 days back
A cross-sectional study evaluates post-intensive care syndrome in cardiac patients 2-4 weeks post-ICU discharge, highlighting cognitive, psychological, and functional impairments and the need for structured multidisciplinary rehabilitation.
3 days back
Anterior cruciate ligament reconstruction failure lacks uniform definition. A narrative review proposes an integrative framework incorporating objective and subjective instability, persistent pain, restricted motion, graft rupture, and secondary meniscal injury to standardize clinical reporting.
3 days back
With World Obesity Atlas data warning that over 41 million Indian children are overweight or obese, ICMR and NIN have unveiled a 10-point policy roadmap. The initiative calls for mandatory front-of-pack labeling, HFSS taxes, strict marketing bans, and healthier school environments to curb non-communicable diseases.
Today
