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Cardiovascular Toxicology

, Volume 11, Issue 3, pp 215–225 | Cite as

Cardioprotective Effects of Hesperetin against Doxorubicin-Induced Oxidative Stress and DNA Damage in Rat

  • P. P. Trivedi
  • S. Kushwaha
  • D. N. Tripathi
  • G. B. JenaEmail author
Article

Abstract

Doxorubicin is a widely used chemotherapeutic agent; however, its clinical uses are limited due to its cardiotoxicity associated with an induction of oxidative stress. This study was aimed to investigate the protective effect of hesperetin against doxorubicin-induced cardiotoxicity in rats. Doxorubicin was administered at the dosage of 4 mg/kg bw/week, ip for a period of 5 consecutive weeks. Hesperetin was administered at the dosages of 25, 50 and 100 mg/kg bw, po by gavage for 5 consecutive days in a week for 5 weeks. The animals were killed 1 week after the last injection of doxorubicin. Hesperetin at the doses of 50 and 100 mg/kg bw significantly reduced MDA and increased GSH levels in the doxorubicin-treated animals. Further, hesperetin significantly reduced doxorubicin-induced DNA damage as well as apoptosis at 25, 50, and 100 mg/kg bw as evident from the comet and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assays, respectively. Thus, hesperetin ameliorated doxorubicin-induced cardiotoxicity by reducing oxidative stress, abnormal cellular morphology and DNA damage in rat. Moreover, nuclear factor-kappa B, p38, and caspase-3 play a role in the hesperetin-mediated protection against doxorubicin-induced cardiotoxicity. This study indicates the protective effect of hesperetin against doxorubicin-induced cardiotoxicity.

Keywords

Doxorubicin Hesperetin Heart Oxidative stress Apoptosis 

Abbreviations

DOX

Doxorubicin

TUNEL

Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling

NFκB

Nuclear factor-kappa B

SD

Sprague–Dawley

CMC

Carboxy methyl cellulose

H&E

Hematoxylin and eosin

EtBr

Ethidium bromide

DMSO

Dimethylsulfoxide

NMPA

Normal melting point agarose

LMPA

Low melting point agarose

EDTA

Ethylenediamine tetraacetic acid

HBSS

Hank’s balanced salt solution

ip

Intraperitoneal

TL

Tail length

TM

Tail moment

OTM

Olive tail moment

% DNA

% DNA in comet tail

MDA

Malondialdehyde

GSH

Reduced glutathione

Notes

Acknowledgments

We wish to acknowledge the financial assistance received from National Institute of Pharmaceutical Education and Research (NIPER), Mohali, to undertake this study. The authors would also like to acknowledge Intas Pharmaceuticals Ltd., Ahmedabad, Gujarat, for benevolently granting the gift sample of doxorubicin.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • P. P. Trivedi
    • 1
  • S. Kushwaha
    • 1
  • D. N. Tripathi
    • 1
  • G. B. Jena
    • 1
    Email author
  1. 1.Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and ResearchS.A.S. NagarIndia

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