Bentley, Robert, Roberts, James A, Saville, Eleanor, Alabdullatif, Shaker, Perkins, David, Fogg, Paislee, Keay, Laura M, Gent, David G, Jenkins, Rosalind E, Rainbow, Richard D 
ORCID: 0000-0002-0532-1992 et al (show 1 more authors)
(2026)
Mitigating doxorubicin cardiotoxicity in isolated cardiomyocytes: The combined role of NRF2 inducers and glucose regulation
Pharmacological Research - Reports, 5.
100086-.
ISSN 2950-2004
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Bentley et al 2026 AC16 paper.pdf - Open Access published version Download (10MB) | Preview |
Abstract
Doxorubicin is a potent chemotherapeutic agent widely used to treat both solid tumours and hematologic malignancies. Despite its clinical efficacy, its use is significantly limited by dose-dependent cardiotoxicity, which restricts cumulative lifetime dosing. While various mechanisms of doxorubicin-induced cardiotoxicity have been proposed, effective strategies for cardioprotection remain scarce. In this study, we investigate the role of elevated glucose levels as a potential exacerbating factor in doxorubicin-induced cardiac toxicity in vitro. Our findings indicate that hyperglycaemic glucose levels may worsen cardiotoxic effects in cardiac cells. Furthermore, we demonstrate that inducing the NRF2 pathway using Bardoxolone methyl, a semi-synthetic triterpenoid, and Fisetin, a dietary flavonoid, confers significant cardioprotection. Notably, we show that combining these NRF2 activators with reduced glucose levels at the time of doxorubicin exposure enhances their protective effects, suggesting a synergistic strategy that may improve outcomes for both cardiac cells in vitro and potentially for patients undergoing chemotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, Heart Disease, Cardiovascular, Nutrition, Cancer, Complementary and Integrative Health, Dietary Supplements, 2.1 Biological and endogenous factors, 6.1 Pharmaceuticals, Cardiovascular |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff) Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Cardiovascular & Metabolic Medicine |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 May 2026 10:50 |
| Last Modified: | 25 Aug 2026 17:15 |
| DOI: | 10.1016/j.prerep.2026.100086 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3198350 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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