Comparative Study on the Protective Effect of Dexrazoxane and Blueberry Extract Against Doxorubicin-induced Cardiotoxicity in Rats

Abstract

<title>Abstract</title> The therapeutic efficacy of anthracycline antibiotic, doxorubicin (DOX), is hampered due to cardiotoxicity. The objective of the study was to explore the counteraction of blueberry (BB) extract and Dexrazoxane (DEX) in Dox-induced cardiotoxicity in Wistar rats.Screening of BB extract as well as DEX for protection the myocardium from Dox-induced oxidative stress was performed on seven groups (8 rats each): Control (normal diet for 14 days and IP injection of normal saline (10 ml/kg) on the 11th day), DOX control (normal diet for 14 days with a single DOX injection of 18 mg/kg on the 11th day), BB extract control (80 mg/kg), DEX (180 mg/kg on the 11th day), BB + DOX (80 mg/kg BB extract for 14 days with DOX on the 11th day, 18 mg/kg), DEX + DOX (180 mg/kg DEX 30 minutes before 18 mg/kg DOX on the 11th day), and a combined group BB + DOX + DEX.A significant increase in serum biomarkers cTnT, NT-proBNP, MPO and cardiac MDA, TOP II, and a significant decrease in GSH and SOD contents were observed in the cardiotoxic (DOX control) group. All these parameters were reversed significantly in all treated groups in comparison to cardiotoxic groups. The cardiotoxic group showed significant upregulation of miR-140-5p expression and significant downregulation of Sirt2 and Nrf2 expression reversed in all treated groups except miR-140-5p which showed unsignificant difference. The best ameliorative effect was observed in the combined group. The histopathological assessment of myocardial damage provided supportive evidence for the biochemical results obtained.In conclusion, the BB extract (80.0 mg/kg) can attenuate the DOX-induced oxidative stress, and it has the potential to be developed as an adjunct against DOX-induced cardiotoxicity in cancer patients who undergo anthracycline chemotherapy.