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Cancer Chemotherapy and Pharmacology

, Volume 74, Issue 3, pp 559–569 | Cite as

Modulatory effects of meloxicam on cardiotoxicity and antitumor activity of doxorubicin in mice

  • Memy H. Hassan
  • Hesham A. El-Beshbishy
  • Hamdy Aly
  • Sabry M. Attia
  • Saleh A. Bahashwan
  • Mohamed M. Ghobara
Original Article

Abstract

Purpose

This study was undertaken to assess the possible modulatory effects and mechanisms of meloxicam, a cyclooxygenase-2 inhibitor, on the antitumor activity and cardiotoxicity of doxorubicin in a mice model of mammary carcinoma.

Methods

Solid tumor mass was developed in female albino mice using Ehrlich carcinoma cells. Forty mice-bearing tumor were divided randomly into four groups for treatment: with saline, meloxicam 10 mg/kg, doxorubicin 5 mg/kg and meloxicam 1 h ahead of doxorubicin, twice weekly for 2 weeks. Tumor volume was followed up and cardiac protective utility was estimated via measuring heart and serum parameters.

Results

Meloxicam expressed a non-significant increase in doxorubicin antitumor activity. Conversely, meloxicam significantly (p < 0.01) mitigated doxorubicin-induced elevation of serum cardiac enzymes [creatine kinase, lactate dehydrogenase and troponin-I]; cardiac lipid peroxidations marker; cardiac active caspase-3 content; and cardiac prostaglandin E2 content. Meloxicam significantly abrogated doxorubicin-induced disturbance in heart histology and relative heart weight to body weight. Meloxicam normalized doxorubicin-induced suppression in heart antioxidant enzymes activities and gene expressions [superoxide dismutase, glutathione peroxidase (GSH-Px) and catalase], and heart GSH content. In addition, meloxicam ameliorated doxorubicin-induced disturbance in phase II metabolizing enzyme, cardiac quinone reductase (QR), at activity level and mRNA expression.

Conclusion

Meloxicam protects heart against doxorubicin toxicity without affecting its antitumor activity against solid mammary cancer model in mice. This protective effect is attributed to antioxidant effect, antiradical effect, antiinflammatory action, antiapoptotic effect and induction of QR enzyme.

Keywords

Doxorubicin Oxidative stress Quinone reductase Cyclooxygenase-2 inhibitors Meloxicam 

Notes

Acknowledgments

We are deeply thankful to the animal house technician Mr. Islam Farouk, Pharm. B.Sc., department of Pharmacology, Faculty of Pharmacy, King Abdel-Aziz University, Jeddah, K.S.A., for his kind accommodation of laboratory animals and support during animal experiment. Also we are indebted to Dr. Fares El-Tom, a lecture of histology at Taibah University, K.S.A., for his invaluable contribution in histological examination of cardiac tissue. The authors disclosed receipt the full financial support and funding from the Deanship of Scientific Research; Taibah University—Almadinah Almunawarah; Saudi Arabia (Grant Number 1091–1433) for this study.

Conflict of interest

All authors have nothing to declare.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Memy H. Hassan
    • 1
    • 2
  • Hesham A. El-Beshbishy
    • 3
    • 4
  • Hamdy Aly
    • 2
    • 5
  • Sabry M. Attia
    • 2
    • 6
  • Saleh A. Bahashwan
    • 1
  • Mohamed M. Ghobara
    • 3
    • 7
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyTaibah UniversityEl-Madinah, El-MunaworahSaudi Arabia
  2. 2.Department of Pharmacology and Toxicology, Faculty of PharmacyAl-Azahr UniversityCairoEgypt
  3. 3.Department of Medical Laboratories Technology, Faculty of Applied Medical SciencesTaibah UniversityEl-Madinah, El-MunaworahSaudi Arabia
  4. 4.Department of Biochemistry, Faculty of PharmacyAl-Azhar UniversityCairoEgypt
  5. 5.Department of Pharmacology and Toxicology, Faculty of PharmacyKing Abdel-Aziz UniversityJeddahSaudi Arabia
  6. 6.Department of Pharmacology and Toxicology, Faculty of PharmacyKing Saud UniversityRiyadhSaudi Arabia
  7. 7.Department of Histology, Faculty of MedicineTanta UniversityTantaEgypt

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