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Updated: Jun 13, 2026

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Protective effect of carvedilol on daunorubicin-induced cardiotoxicity and nephrotoxicity in rats
Wawaimuli Arozal1, Kenichi Watanabe, Punniyakoti T Veeraveedu
1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima Akiha-ku, Niigata City 956-8603, Japan.
Abstract:
Daunorubicin (DNR) is one of the anthracycline anti-tumor agents widely used in the treatment of acute myeloid leukemia. However, the clinical use of DNR has been limited by its undesirable systemic toxicity, especially in the heart and kidney. This study was designed to test the effectiveness of carvedilol, a nonselective beta-blocker against DNR-induced cardiotoxicity and nephrotoxicity. Rats were treated with a cumulative dose of 9 mg/kg body weight DNR (i.v.). Carvedilol was administered orally every day for 6 weeks. DNR rats showed cardiac and nephrotoxicities as evidenced by worsening cardiac and kidney functions, which were evaluated by hemodynamic and echocardiographic studies, and by measuring protein in urine, levels of urea and creatinine in serum, lipid profiles, malondialdeyde level and the total level of glutathione peroxidase activity in both heart and kidney tissues. These changes were reversed by treatment with carvedilol, which resulted in significant improvement in the cardio-renal function. Furthermore, carvedilol down-regulated matrix metalloproteinase-2 expression in the heart, increased nephrin expression in the kidney, and attenuated the increased protein expression of NADPH oxidase subunits in heart and kidney. Moreover, carvedilol reduced myocardial and renal apoptosis and improved the histopathological changes in heart and kidney induced by DNR. In conclusion, the present study demonstrated a beneficial effect of carvedilol treatment in the prevention of DNR-induced cardiotoxicity and nephrotoxicity by reversing the oxidative stress and apoptosis.
Insights
Carvedilol effectively prevents heart and kidney damage caused by the chemotherapy drug daunorubicin (DNR). This study shows carvedilol reverses DNR
Area of Science:
- Pharmacology
- Cardiology
- Nephrology
Background:
- Daunorubicin (DNR) is a key chemotherapy agent for acute myeloid leukemia.
- DNR's clinical utility is restricted by significant cardiotoxicity and nephrotoxicity.
- Effective strategies to mitigate DNR-induced organ damage are urgently needed.
Purpose of the Study:
- To investigate the protective effects of carvedilol against daunorubicin-induced cardiotoxicity and nephrotoxicity.
- To elucidate the underlying mechanisms of carvedilol's renoprotective and cardioprotective actions.
Main Methods:
- Rats received a cumulative dose of 9 mg/kg daunorubicin (i.v.).
- Carvedilol was administered orally daily for 6 weeks.
- Cardio-renal function, oxidative stress markers, apoptosis, and histopathology were assessed.
Main Results:
- Daunorubicin induced significant cardiotoxicity and nephrotoxicity, evidenced by impaired function and elevated biomarkers.
- Carvedilol treatment reversed these toxicities, improving hemodynamic and echocardiographic parameters.
- Carvedilol reduced oxidative stress, matrix metalloproteinase-2 and NADPH oxidase expression, and apoptosis, while increasing nephrin expression.
Conclusions:
- Carvedilol demonstrates significant cardioprotective and renoprotective effects against daunorubicin-induced toxicity.
- The protective mechanisms involve mitigating oxidative stress, inflammation, and apoptosis in cardiac and renal tissues.
- Carvedilol represents a promising therapeutic strategy to enhance the safety profile of daunorubicin chemotherapy.
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