Antioxidant, antiapoptotic, and antifibrotic effects of the combination of liposomal resveratrol and carvedilol against doxorubicin‐induced cardiomyopathy in rats

• Published in: Journal of biochemical and molecular toxicology 2020-07, Vol.34 (7), p.e22492-n/a
• Main Authors: Alanazi, Abeer, Fadda, Laila, Alhusaini, Ahlam, Ahmad, Rehab
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics; Antibiotics, Antineoplastic - adverse effects; Antioxidants; Antioxidants - administration & dosage; Apoptosis - drug effects; Body weight; Calcium-binding protein; Cardiomyopathies - chemically induced; Cardiomyopathies - drug therapy; Cardiomyopathy; Cardiotoxicity; Cardiotoxicity - drug therapy; carvedilol; Carvedilol - administration & dosage; Caspase; Caspase 3 - metabolism; Creatine; Creatine kinase; Cytotoxicity; Doxorubicin; Doxorubicin - adverse effects; Drug Therapy, Combination; Glutathione; Heart - drug effects; Kinases; liposomal resveratrol; Liposomes; Male; Myocardium - metabolism; NF-kappa B - metabolism; Parameters; Rats; Rats, Wistar; Resveratrol; Resveratrol - administration & dosage; Signal Transduction - drug effects; Superoxide dismutase; Transforming Growth Factor beta1 - metabolism; Troponin
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.22492

The use of the cytotoxic antibiotic doxorubicin (DOXR) is limited by its dose‐dependent cardiotoxicity. The aim of this study was to evaluate the cardioprotective effect of the combination of carvedilol (CARD) and liposomal resveratrol (LIPO RESV) against DOXR‐induced cardiomyopathy in rats. The results of the present study showed that DOXR administration significantly increased heart weight/body weight ratio by 35.6%, creatine kinase‐MB (CK‐MB) by 40.6%, troponin‐I levels by 85%, and decreased reduced glutathione level and superoxide dismutase activity by 47% and 52%, respectively compared to the control group. Moreover, cardiac caspase‐3 protein expression was upregulated by 51.6% vs the control group. In contrast, treatment of DOXR‐administered rats with CARD, RESV, or LIPO RESV and their combination for 6 weeks improved all the above‐mentioned measured parameters. In conclusion, concomitant administration of CARD and LIPO RESV exerted additive pharmacological effects in some measured parameters against DOXR‐induced cardiomyopathy and this may be a useful cardioprotective strategy.