Animal study of Anthracycline-induced Cardiotoxicity and Nephrotoxicity and Evaluation of Protective Agents

Amani N Shafik,Mostafa M Khodeir,Mostafa S Fadel

doi:10.4172/1948-5956.1000068

Amani N Shafik, Mostafa M Khodeir + Show 1 more

Open Access

https://doi.org/10.4172/1948-5956.1000068

Copy DOI

Abstract

Study background: Anticancer chemotherapy Anthracycline (ANT) antibiotics associated with cardiac and renal toxicity which represents serious complication. In this study, the protective effect of the 2 beta-blockers carvedilol and nebivolol were tested in a rat model of ANT induced cardio and renal-toxicity by repeated intraperitoneal doxorubicin (Dox) administration. Methods: Six groups of animals were used, each 8 rats divided as control group- received intraperitoneal saline every other day; control carvedilol: rats received carvedilol dose 30mg/kg/day orally; control nebivolol: rats received nebivolol 1mg/kg/day orally; doxorubicin alone: a dose of 3 mg/kg/day was administered intraperitoneal every other day; doxorubicin + carvedilol: carvedilol started at the same day with Dox; doxorubicin + nebivolol: nebivolol started at the same day with Dox. All substances were administered for 12 days. Detection & quantification of doxorubicin-induced heart and renal damage and therapeutic action of beta-blockers was done using Langendorff's technique, echo-cardiographic function examinations, serum creatinine, total proteins and histopathology. Results: The administration of doxorubicin in the dose of 3 mg/kg/day for 12 days produced pronounced heart impairment, as well as renal nephrotoxic changes. Significant reduction of Doxo-cardiotoxicity and nephrotoxicity in Nebivolol-treated animals more than Carvedilol treated animals. Conclusions: Coadministration of either carvedilol or nebivolol with doxorubicin was able to ameliorate up to almost contradict doxorubicin-induced myocardial injury, glomerular filtration disturbance and renal tubular damage with upper hand for nebivolol. So, they can be considered a feasible candidate to protect against nephrotoxicity & cardiotoxicity commonly encountered with doxorubicin treatment.

Highlights

Doxorubicin (Dox) is one of the most potent broad-spectrum antitumor anthracycline antibiotics, widely used to treat a variety of cancers including breast, ovarian, lung, uterine and cervical cancers, Hodgkin’s disease, non-Hodgkin lymphoma, acute leukemia, soft tissue and primary bone sarcomas [1,2,3]
Dox–nebivolol treated group showed significant decrease in levels of creatinine compared to dox alone group (p=0.0006), it showed significant lower creatinine levels compared to dox-carvedilol treated group (p=0.0002) (Figure 1a)
Doxorubicin therapy was shown to decrease total proteins significantly after 12 days as compared to the control values (p

Summary

Introduction

Doxorubicin (Dox) is one of the most potent broad-spectrum antitumor anthracycline antibiotics, widely used to treat a variety of cancers including breast, ovarian, lung, uterine and cervical cancers, Hodgkin’s disease, non-Hodgkin lymphoma, acute leukemia, soft tissue and primary bone sarcomas [1,2,3]. Because of their great importance in cancer therapy, researchers have expended great efforts trying to prevent or attenuate the side effects of Dox administration. These chemicals includes natural Products e.g. the most commonly used and investigated compounds are vitamins (E, C, A, carotenoids), coenzyme Q, flavonoids, polyphenols, herbal antioxidants, selenium, and virgin olive oil [7]

Methods

Results

Discussion

Conclusion