Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Shivani Wagh; Kalpesh Patil; Umesh Mahajan; Pradnya Bagal; Avinash Wadkar; Chandragouda Patil; Basavraj Bommanhalli; Prabhakar Patil; Sameer Goyal; Shreesh Ojha; Chandragouda Patil

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Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Author: Shivani WAGH ¹ ; Kalpesh PATIL ¹ ; Umesh MAHAJAN ¹ ; Pradnya BAGAL ¹ ; Avinash WADKAR ¹ ; Chandragouda PATIL ¹ ; Basavraj BOMMANHALLI ² ; Prabhakar PATIL ³ ; Sameer GOYAL ^{4
,

5} ; Shreesh OJHA ⁶ ; Chandragouda PATIL ⁷
Author Information

1. Department Of Pharmacology, R. C. Patel Institute Of Pharmaceutical Education And Research
2. Department Of Pathology, Gadag Institute Of Medical Sciences
3. Department Of Pharmacology, Navodaya Medical College
4. Shri Vile Parle Kelavani Mandal'
5. s Institute Of Pharmacy
6. Department Of Pharmacology And Therapeutics, College Of Medicine And Health Sciences, United Arab Emirates University
7. Department Of Pharmacology, Delhi Pharmaceutical Sciences And Research University
Publication Type:Journal Article
Keywords: Cardiac injury; Cardiotoxicity; Chemoprevention; Doxorubicin; Genistein; Hemodynamic changes; Phloretin; Phytoestrogens
From:Asian Pacific Journal of Tropical Biomedicine 2022;12(3):124-131
CountryChina
Language:English
Abstract: Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.