Tags

Type your tag names separated by a space and hit enter

Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model.
Cancer Chemother Pharmacol 2009; 63(2):343-9CC

Abstract

PURPOSE

Dexrazoxane (DZR), a clinically approved cation chelator, is effective in reducing doxorubicin (DOX)-induced heart damage, yet its cardioprotective mechanism is not fully understood. We aimed to investigate the effects of DZR on the activation of Akt and Erk 1/2 signals in a rat model of DOX-induced cardiomyopathy.

METHODS

Male Sprague-Dawley rats received weekly DOX injection (2.5 mg/kg) for 6 weeks, with or without DZR pretreatment at a dose ratio of 20:1. The ventricular functions of these animals were monitored at week 6, 9 and 11 by echocardiography. At week 11, their heart morphology was studied by light and electron microscopy. Phosphorylation of Akt and Erk in heart tissues was measured by Western blot analysis.

RESULTS

DOX caused myocardial damage with compromised left ventricular function, increased myocardium injury and reduced phosphorylation of Akt and Erk. DZR exerted a significant cardioprotective effect in terms of improved fractional shortening, cardiac output and cardiomyopathy score at one or more time points. We also provided the first evidence that dexarazoxane-treated animals had increased levels of Akt and Erk activation, whilst total Akt and Erk remained unchanged.

CONCLUSIONS

Our results showed that the cardioprotective effect of dexarazoxane has been sustained beyond the treatment period. The data also suggested that activation of the Akt and Erk signaling pathways was regulated in the course of DOX-induced cardiomyopathy and protection by DZR.

Authors+Show Affiliations

Department of Cardiology, Children's Hospital of Chongqing Medical University, Chongqing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18379782

Citation

Xiang, Ping, et al. "Dexrazoxane Protects Against Doxorubicin-induced Cardiomyopathy: Upregulation of Akt and Erk Phosphorylation in a Rat Model." Cancer Chemotherapy and Pharmacology, vol. 63, no. 2, 2009, pp. 343-9.
Xiang P, Deng HY, Li K, et al. Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. Cancer Chemother Pharmacol. 2009;63(2):343-9.
Xiang, P., Deng, H. Y., Li, K., Huang, G. Y., Chen, Y., Tu, L., ... Sung, R. Y. (2009). Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. Cancer Chemotherapy and Pharmacology, 63(2), pp. 343-9. doi:10.1007/s00280-008-0744-4.
Xiang P, et al. Dexrazoxane Protects Against Doxorubicin-induced Cardiomyopathy: Upregulation of Akt and Erk Phosphorylation in a Rat Model. Cancer Chemother Pharmacol. 2009;63(2):343-9. PubMed PMID: 18379782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. AU - Xiang,Ping, AU - Deng,Hai Yan, AU - Li,Karen, AU - Huang,Guo-Ying, AU - Chen,Yuan, AU - Tu,Liu, AU - Ng,Pak Cheung, AU - Pong,Nga Hin, AU - Zhao,Hailu, AU - Zhang,Lei, AU - Sung,Rita Yn Tz, Y1 - 2008/04/01/ PY - 2007/12/04/received PY - 2008/03/17/accepted PY - 2008/4/2/pubmed PY - 2008/12/23/medline PY - 2008/4/2/entrez SP - 343 EP - 9 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother. Pharmacol. VL - 63 IS - 2 N2 - PURPOSE: Dexrazoxane (DZR), a clinically approved cation chelator, is effective in reducing doxorubicin (DOX)-induced heart damage, yet its cardioprotective mechanism is not fully understood. We aimed to investigate the effects of DZR on the activation of Akt and Erk 1/2 signals in a rat model of DOX-induced cardiomyopathy. METHODS: Male Sprague-Dawley rats received weekly DOX injection (2.5 mg/kg) for 6 weeks, with or without DZR pretreatment at a dose ratio of 20:1. The ventricular functions of these animals were monitored at week 6, 9 and 11 by echocardiography. At week 11, their heart morphology was studied by light and electron microscopy. Phosphorylation of Akt and Erk in heart tissues was measured by Western blot analysis. RESULTS: DOX caused myocardial damage with compromised left ventricular function, increased myocardium injury and reduced phosphorylation of Akt and Erk. DZR exerted a significant cardioprotective effect in terms of improved fractional shortening, cardiac output and cardiomyopathy score at one or more time points. We also provided the first evidence that dexarazoxane-treated animals had increased levels of Akt and Erk activation, whilst total Akt and Erk remained unchanged. CONCLUSIONS: Our results showed that the cardioprotective effect of dexarazoxane has been sustained beyond the treatment period. The data also suggested that activation of the Akt and Erk signaling pathways was regulated in the course of DOX-induced cardiomyopathy and protection by DZR. SN - 1432-0843 UR - https://www.unboundmedicine.com/medline/citation/18379782/Dexrazoxane_protects_against_doxorubicin_induced_cardiomyopathy:_upregulation_of_Akt_and_Erk_phosphorylation_in_a_rat_model_ L2 - https://dx.doi.org/10.1007/s00280-008-0744-4 DB - PRIME DP - Unbound Medicine ER -