Ahmed Kabel

Egypt

Fraxetin mitigates doxorubicin-induced cardiotoxicity

Ahmed M. Kabel1, Samir A. Salama2, Almokhtar A. Adwas3, Aya A. Kabel4, Remon S. Estfanous5

1. Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
2. Division of Biochemistry, Department of Pharmacology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
3. Department of Pharmacology, Faculty of Medicine, Sabratha University, Sabratha P.O. Box 250, Libya
4. Faculty of Medicine, Mansoura University, Mansoura, Egypt
5. Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt

Abstract

Background

Doxorubicin belongs to the class of anthracycline antibiotics that is widely used in the
treatment protocols of a wide range of malignancies. The major deleterious effect of doxorubicin use is the possible occurrence of cardiotoxicity.

Methods

This study aimed to delineate the possible effects of targeting oxidative stress, NLRP3 inflammasome, and autophagy by fraxetin on doxorubicin‐induced cardiac dysfunction in rats.

Results

In a model of doxorubicin‐induced cardiotoxicity, the effects of different doses of fraxetin were assessed by determination of biochemical, histopathological, immunohistochemical, and electron microscopic changes. Fraxetin, in a dose‐dependent manner, was found to have the ability to mitigate the harmful effects of oxidative stress and inflammation on myocardial muscles with significant decrease in NLRP3 inflammasome, augmentation of autophagy, and amelioration of the apoptotic signaling pathways. In addition, fraxetin, in
a dose‐dependent manner, had the ability to combat the echocardiographic, histopathological, immunohistochemical, and electron microscopic changes induced by doxorubicin in cardiomyocytes.

Conclusions

Fraxetin may represent a new adjuvant line of therapy for mitigation of doxorubicin‐induced cardiotoxicity