Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals

Cancer Cell International

Osman H Osman⁶  Zoheir A Damanhouri⁶  Huda M Al-Kreathy⁶  Mohamed N Alaama⁴  Wafaa S Ramadan¹  Mohamed F Elshal³  Ohoud M AlArabi⁶  Sameer E Al-Harthi⁵  Abdel-Moneim M Osman² 

[1] Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;National Cancer Institute, Cairo University, Cairo, Egypt;Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medicine, Cardiology unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Jeddah, Saudi Arabia;Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

关键词: Cell cycle disturbance;    Cardioprotection;    Potentiation;    Resveratrol;    Doxorubicin;   

Others  :  793711
DOI  :  10.1186/1475-2867-13-52

 received in 2013-02-25, accepted in 2013-05-14,  发布年份 2013

【 摘 要 】

Background

Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer drug used in the treatment of variety of cancers .Its use is limited by its cardiotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of DOX and at the same time its protective effect against DOX-induced cardiotoxicity in rats.

Methods

Ehrlich ascites carcinoma bearing mice were used in this study. Percent survival of tumor bearing mice was used for determination of the Cytotoxic activity of DOX in presence and absence of RSVL. Uptake and cell cycle effect of DOX in tumor cells in the presence of RSVL was also determined. Histopatholgical examination of heart tissues after DOX and/or RSVL therapy was also investigated.

Results

DOX at a dose level of 15 mg/kg increased the mean survival time of tumor bearing mice to 21 days compared with 15 days for non tumor-bearing control mice. Administration of RSVL at a dose level of 10 mg/kg simultaneously with DOX increased the mean survival time to 30 days with 70% survival of the tumor-bearing animals. RSVL increased the intracellular level of DOX and there was a strong correlation between the high cellular level of DOX and its cytotoxic activity. Moreover, RSVL treatment showed 4.8 fold inhibition in proliferation index of cells treated with DOX. Histopathological analysis of rat heart tissue after a single dose of DOX (20 mg/kg) showed myocytolysis with congestion of blood vessels, cytoplasmic vacuolization and fragmentation. Concomitant treatment with RSVL, fragmentation of the muscle fiber revealed normal muscle fiber.

Conclusion

This study suggests that RSVL could increase the cytotoxic activity of DOX and at the same time protect against its cardiotoxicity.

【 授权许可】

   
2013 Osman et al.; licensee BioMed Central Ltd.

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