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The Korean Journal of Pathology 2004;38(6): 378-387.
Effect of Probucol and Verapamil on Injury to Myocardium and Nerve Fibers in Rat Heart Induced by Doxorubicin.
Sang Yeop Yi, Sang Ho Cho, Woo Ick Yang
1Department of Pathology, Kwandong University College of Medicine, Goyang, Korea.
2Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. wiyang9660@yumc.yonsei.ac.kr
ABSTRACT
BACKGROUND: Doxorubicin is considered to be one of the most effective drugs to treat a variety of human cancers. However, the dose-dependent cardiotoxicity of doxorubicin limits its clinical usefulness. This study aimed to evaluate the effect of probucol and verapamil on the cardiac neurotoxicity and cardiomyopathy induced by the long-term use of doxorubicin. METHODS: Sprague-Dawley male rats were grouped as the control group, the doxorubicin treated group, the doxorubicin treated with probucol group, and the doxorubicin treated with verapamil group. The rats were treated for 4, 6, 8 and 10 weeks. H&E staining and immunohistochemical staining for protein gene product 9.5, caspase-3, heat shock protein 70, and hsp 25 were performed. RESULTS: The degree of interstitial inflammatory cell infiltration was mildest in the probucol treated group. The reduction in the number of nerve fibers in the probucol treated group was less than the other treatment groups. There was a negative correlation between the treatment duration and stained nerve fibers in all the treatment groups. The number of caspase-3 positive cells was more increased in the doxorubicin group and the verapamil treated group than in the control and probucol treated group. CONCLUSION: It is suggested that probucol partly contributed to the inhibition of doxorubicin-induced cardiac neurotoxicity and cardiomyopathy, whereas the verapamil had no effect.
Key Words: Doxorubicin; Probucol; Cardiomyopathies; PGP 9.5 protein, rat; Caspase-3
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