Cardioprotective effects of rosuvastatin and carvedilol on delayed cardiotoxicity of doxorubicin in rats

Yong Hyun Kim, Seong Mi Park, Mina Kim, Seong Hwan Kim, Sang Yeob Lim, Jeong Cheon Ahn, Woo Hyuk Song, Wan Joo Shim

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Context: 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. Discussion and 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.

Original languageEnglish
Pages (from-to)488-498
Number of pages11
JournalToxicology Mechanisms and Methods
Volume22
Issue number6
DOIs
Publication statusPublished - 2012 Jul

Keywords

  • Anthracycline cardiomyopathy
  • antioxidant
  • malondialdehyde
  • malondialdehyde to oxidative stress
  • myocardial fibrosis
  • statin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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