Lab Anim Res.  2017 Jun;33(2):165-170. 10.5625/lar.2017.33.2.165.

Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources

• Kim SH
• Kim KJ
• Kim JH
• Kwak JH
• Song H
• Cho JY
• Hwang DY
• Kim KS
• Jung YS

• KMID: 2407431
• DOI: http://doi.org/10.5625/lar.2017.33.2.165

Abstract

Doxorubicin is a widely used chemotherapeutic agents and is now part of standard therapeutic regimens for a variety of cancers (eg, hematopoietic malignancies and advanced solid tumors of the breast, ovary, thyroid, and bone). However, a potentially lethal and dose-dependent cardiotoxicity that appears within a short time after treatment limits the usage of doxorubicin in cancer patients. Although the mechanism of doxorubicin-induced cardiotoxicity is not completely understood, it is thought that free radical-induced oxidative stress and excessive production of reactive oxygen species are primary drivers of its toxicity. In this study, we compared the doxorubicin-induced cardiotoxicity of ICR mice obtained from three different sources and evaluated the utility of Korl:ICR stock established by the Korean FDA. Because doxorubicin-induced cardiotoxicity is thought to involve the excessive generation of ROS followed by oxidative stress, we determined the representative tissue index of oxidation, lipid peroxidation, and antioxidant, glutathione (GSH), as well as the parameters of heart injury. Doxorubicin treatment successfully induced cardiotoxicity as evidenced by histological examination and serum parameters (eg, levels of LDH and CK activities) in ICR mice. It was accompanied by increased lipid peroxidation and a decrease in both cysteine and GSH, further supporting previous reports that oxidative stress is a potential mechanism of doxorubicin-induced cardiotoxicity. Of interest, we did not observe a significant difference in doxorubicin-induced cardiotoxicity among mice of different origins. Collectively, our results suggest that Korl:ICR strain may be useful in the research of doxorubicin-induced cardiotoxicity.

Keyword

Cardiotoxicity; doxorubicin; oxidative stress; ICR mouse

MeSH Terms

Animals
Breast
Cardiotoxicity*
Cysteine
Doxorubicin
Female
Glutathione
Heart Injuries
Hematologic Neoplasms
Humans
Lipid Peroxidation
Mice
Mice, Inbred ICR*
Ovary
Oxidative Stress
Reactive Oxygen Species
Thyroid Gland
Cysteine
Doxorubicin
Glutathione
Reactive Oxygen Species

Figure

• 

  Figure 1 Effects of doxorubicin (DOX) treatment on LDH (A) and CK-MB (B) activities in the heart of ICR mice. **, *** Significantly different from the corresponding control mice (ANOVA followed by Newman-Keuls multiple range test, P<0.01, 0.001, respectively).

• 

  Figure 2 Histopathological changes in cardiac tissue following doxorubicin (DOX) treatment in ICR mice from three different sources. Pictures of heart sections from the control (A, C, and E) and DOX-treated (B, D, and F). Original magnification, ×100.

• 

  Figure 3 Effects of doxorubicin (DOX) treatment on MDA levels in the heart of ICR mice. *** Significantly different from the corresponding control mice (ANOVA followed by Newman-Keuls multiple range test, P<0.001).

• 

  Figure 4 Changes in the levels of cysteine (A) and GSH (B) in the heart of doxorubicin (DOX)-treated ICR mice. **, *** Significantly different from the corresponding control mice (ANOVA followed by Newman-Keuls multiple range test, P<0.01, 0.001, respectively).

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