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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalAsian Pacific Journal of Tropical Biomedicine
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 1 2022

Keywords

  • Cardiac injury
  • Cardiotoxicity
  • Chemoprevention
  • Doxorubicin
  • Genistein
  • Hemodynamic changes
  • Phloretin
  • Phytoestrogens

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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