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

    28 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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