title: Beneficial role of tamoxifen in experimentally induced cardiac hypertrophy.
abstract: BACKGROUND
  Protein kinase C (PKC) activation is associated with cardiac hypertrophy (CH), fibrosis, inflammation and cardiac dysfunction. Tamoxifen is a PKC inhibitor. Despite these, reports on effect of tamoxifen on cardiac hypertrophy are not available. Hence, we have investigated effect of tamoxifen (2mg/kg/day, po) on CH.
  
  
  METHODS
  In isoproterenol (ISO) induced CH, ISO (5mg/kg/day, ip) was administered for 10 days in Wistar rats. For partial abdominal aortic constriction (PAAC), abdominal aorta was ligated by 4-0 silk thread around 7.0mm diameter blunt needle. Then the needle was removed to leave the aorta partially constricted for 30 days. Tamoxifen was given for 10 days and 30 days, respectively, in ISO and PAAC models and at end of each studies, animals were sacrificed and biochemical and cardiac parameters were evaluated.
  
  
  RESULTS
  ISO and PAAC produced significant dyslipidemia, hypertension, bradycardia, oxidative stress and increase in serum lactate dehydrogenase and creatine kinase-MB, C-reactive protein. Treatment with tamoxifen significantly controlled dyslipidemia, hypertension, bradycardia, oxidative stress and reduced serum cardiac markers. ISO control and PAAC control rats exhibited significantly increased cardiac and left ventricular (LV) hypertrophic index, LV thickness, cardiomyocyte diameter. Treatment with tamoxifen significantly reduced these hypertrophic indices. There was a significant increase in LV collagen level, decrease in Na(+)K(+)ATPase activity, and reduction in the rate of pressure development and decay. Tamoxifen significantly reduced LV collagen, increased Na(+)K(+)ATPase activity and improved hemodynamic function. This was further supported by histopathological studies, in which tamoxifen showed marked decrease in fibrosis and increase in extracellular spaces in the treated animals.
  
  
  CONCLUSIONS
  Our data suggest that tamoxifen produces beneficial effects on cardiac hypertrophy and hence may be considered as a preventive measure for cardiac hypertrophy.
authors.affiliation: Institute of Pharmacy, Nirma University, Ahmedabad, India. Electronic address: drbhoomikampatel@gmail.com.
authors.forename: Bhoomika M
authors.initials: BM
authors.lastname: Patel
authors.affiliation: Institute of Pharmacy, Nirma University, Ahmedabad, India.
authors.forename: Vishal J
authors.initials: VJ
authors.lastname: Desai
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D006332:Cardiomegaly / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D032383:Myocytes, Cardiac / Q000473:pathology; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D008077:Lipoproteins, LDL; D013629:Tamoxifen; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D007545:Isoproterenol
keywords: Cardiac hypertrophy; Isoproterenol (ISO); Partial abdominal aortic constriction (PAAC); Tamoxifen