title: Chemosensetizing and cardioprotective effects of resveratrol in doxorubicin- treated animals.
abstract: 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.
  
  
  CONCLUSIONS
  This study suggests that RSVL could increase the cytotoxic activity of DOX and at the same time protect against its cardiotoxicity.
authors.affiliation: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia ; National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Abdel-Moneim M
authors.initials: AM
authors.lastname: Osman
authors.affiliation: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia ; Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Jeddah, Saudi Arabia.
authors.forename: Sameer E
authors.initials: SE
authors.lastname: Al-Harthi
authors.affiliation: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ohoud M
authors.initials: OM
authors.lastname: AlArabi
authors.affiliation: Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Jeddah, Saudi Arabia ; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Elshal
authors.affiliation: Molecular biology Department, Genetic engineering and Biotechniology Department, Minoufia University, Minoufia, Egypt ; Department of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Wafaa S
authors.initials: WS
authors.lastname: Ramadan
authors.affiliation: Department of Medicine, Cardiology unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Alaama
authors.affiliation: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Huda M
authors.initials: HM
authors.lastname: Al-Kreathy
authors.affiliation: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Zoheir A
authors.initials: ZA
authors.lastname: Damanhouri
authors.affiliation: Pharmacology Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Osman H
authors.initials: OH
authors.lastname: Osman
keywords: Cardioprotection; Cell cycle disturbance; Doxorubicin; Potentiation; Resveratrol