Doxorubicin투여 백서 심장의 심근과 신경 손상에 대한 Probucol과 Verapamil의 효과
Effect of Probucol and Verapamil on Injury to Myocardium and Nerve Fibers in Rat Heart Induced by Doxorubicin
이상엽, 양우익, 조상호,
소속 상세정보
이상엽 ( Yi Sang-Yeop )
관동대학교 의과대학 병리학교실
양우익 ( Yang Woo-Ick )
연세대학교 의과대학 병리학교실
조상호 ( Cho Sang-Ho )
연세대학교 의과대학 병리학교실
KMID : 0357920040380060378
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.
Conclusions: It is suggested that probucol partly contributed to the inhibition of doxorubicin-induced cardiac neurotoxicity and cardiomyopathy, whereas the verapamil had no effect.
키워드
Doxorubicin;Probucol;Cardiomyopathies;PGP 9.5 protien;rat;Caspase-3
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