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

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...

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Main Authors: Sou Hyun Kim, Keuk-Jun Kim, Joung-Hee Kim, Jae-Hwan Kwak, HyunKeun Song, Joon Young Cho, Dae Youn Hwang, Kil Soo Kim, Young-Suk Jung
Format: Article
Language:English
Published: BMC 2017-12-01
Series:Laboratory Animal Research
Subjects:
Online Access:http://link.springer.com/article/10.5625/lar.2017.33.2.165
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author Sou Hyun Kim
Keuk-Jun Kim
Joung-Hee Kim
Jae-Hwan Kwak
HyunKeun Song
Joon Young Cho
Dae Youn Hwang
Kil Soo Kim
Young-Suk Jung
author_facet Sou Hyun Kim
Keuk-Jun Kim
Joung-Hee Kim
Jae-Hwan Kwak
HyunKeun Song
Joon Young Cho
Dae Youn Hwang
Kil Soo Kim
Young-Suk Jung
author_sort Sou Hyun Kim
collection DOAJ
description 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.
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spelling doaj.art-42a92f0de7064a008eeeb2b59c11b64e2022-12-21T19:40:51ZengBMCLaboratory Animal Research2233-76602017-12-0133216517010.5625/lar.2017.33.2.165Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sourcesSou Hyun Kim0Keuk-Jun Kim1Joung-Hee Kim2Jae-Hwan Kwak3HyunKeun Song4Joon Young Cho5Dae Youn Hwang6Kil Soo Kim7Young-Suk Jung8College of Pharmacy, Pusan National UniversityDepartment of Biomedical Laboratory Science, Daekyeung CollegeDepartment of Biomedical Laboratory Science, Daekyeung CollegeCollege of Pharmacy, Kyungsung UniversityDepartment of Microbiology and Immunology, INJE University College of MedicineExercise Biochemistry Laboratory, Korea National Sport UniversityDepartment of Biomaterials Science, College of Natural Resources & Life Science/Life and Industry Convergence Research Institute, Pusan National UniversityCollege of Veterinary Medicine, Kyungpook National UniversityCollege of Pharmacy, Pusan National UniversityAbstract 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.http://link.springer.com/article/10.5625/lar.2017.33.2.165Cardiotoxicitydoxorubicinoxidative stressICR mouse
spellingShingle Sou Hyun Kim
Keuk-Jun Kim
Joung-Hee Kim
Jae-Hwan Kwak
HyunKeun Song
Joon Young Cho
Dae Youn Hwang
Kil Soo Kim
Young-Suk Jung
Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
Laboratory Animal Research
Cardiotoxicity
doxorubicin
oxidative stress
ICR mouse
title Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
title_full Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
title_fullStr Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
title_full_unstemmed Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
title_short Comparision of doxorubicin-induced cardiotoxicity in the ICR mice of different sources
title_sort comparision of doxorubicin induced cardiotoxicity in the icr mice of different sources
topic Cardiotoxicity
doxorubicin
oxidative stress
ICR mouse
url http://link.springer.com/article/10.5625/lar.2017.33.2.165
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