title: Cardioprotective effects of rosuvastatin and carvedilol on delayed cardiotoxicity of doxorubicin in rats.
abstract: BACKGROUND
  Doxorubicin is widely used anti-neoplastic drug but has serious cardiotoxicity. Long-term cardioprotective effects of statin and carvedilol against delayed cardiotoxicity of doxorubicin was not well elucidated.
  
  
  OBJECTIVE
  To evaluate long-term cardioprotective effects of co-administered rosuvastatin and carvedilol against chronic doxorubicin-induced cardiomyopathy (DIC) in rats.
  
  
  METHODS
  Sixty-one rats were assigned to six groups: group I, control; group II, doxorubicin only (1.25 mg/kg, bi-daily, I.P.); group III, doxorubicin + rosuvastatin (2 mg/kg/day, P.O.); group IV, doxorubicin + rosuvastatin(10 mg/kg/day, P.O.); group V, doxorubicin + carvedilol (5 mg/kg/day, P.O.); group VI, doxorubicin + carvedilol (10 mg/kg/day, P.O.). Drugs were administered for 4 weeks (by week 4) and rats were observed without drugs for 4 weeks (by week 8).
  
  
  RESULTS
  After 4 weeks discontinuation of drugs (week 8), group III showed higher +dP/dt (p = 0.058), lower -dP/dt (p = 0.009), lower left ventricular (LV) tissue malondialdehyde (MDA; p = 0.022), and less LV fibrosis (p = 0.011) than group II. Group IV showed similar results to group III. However, in group V and VI, carvedilol failed to reduce LV dysfunction, elevation of troponin or myocardial fibrosis, although group V showed lower LV tissue MDA (p = 0.004) than group II.
  
  
  CONCLUSIONS
  Myocardial injury and LV systolic/diastolic dysfunction at week 8 was alleviated by co-administered rosuvastatin, but not by carvedilol. It is unclear whether the cardioprotective effect of rosuvastatin is attributed to a suppression of oxidative stress induced by doxorubicin, because carvedilol did not exhibit a cardioprotective effect despite its antioxidant effects.
authors.affiliation: Division of Cardiology, Department of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Yong-Hyun
authors.initials: YH
authors.lastname: Kim
authors.forename: Seong-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Mina
authors.initials: M
authors.lastname: Kim
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Lim
authors.forename: Jeong-Cheon
authors.initials: JC
authors.lastname: Ahn
authors.forename: Woo-Hyuk
authors.initials: WH
authors.lastname: Song
authors.forename: Wan-Joo
authors.initials: WJ
authors.lastname: Shim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002227:Carbazoles / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000077261:Carvedilol; D004317:Doxorubicin / Q000633:toxicity*; D004452:Echocardiography; D005464:Fluorobenzenes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress; D011412:Propanolamines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D002316:Cardiotonic Agents; D005464:Fluorobenzenes; D011412:Propanolamines; D011743:Pyrimidines; D013449:Sulfonamides; D000077261:Carvedilol; D004317:Doxorubicin; D000068718:Rosuvastatin Calcium