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Protective Effect of Probucol against Adriamycin-Induced Apoptosis in Cultured Rat Cardiac Myocytes

Journal of the Korean Pediatric Society 2000;43(6):746-754.
Published online June 15, 2000.
Protective Effect of Probucol against Adriamycin-Induced Apoptosis in Cultured Rat Cardiac Myocytes
Sun-Ju Lee1, Dong-Seok Lee1, Yong-Wook Jung2
1Department of Pediatrics, College of Medicine, Dongguk University, Kyungju, Korea
2Department of Anatomy, College of Medicine, Dongguk University, Kyungju, Korea
신생 백서 심근 세포 배양에서 Adriamycin 유도성 Apoptosis에 대한 Probucol의 예방 효과
이선주1, 이동석1, 정용욱2
1동국대학교 의과대학 소아과학교실
2동국대학교 의과대학 해부학교실
Correspondence: 
Sun-Ju Lee, Email: lds117@dumc.or.kr
Abstract
Purpose
: In adriamycin(ADR)-induced cardiomyopathy, several different mechanisms are suggested. However, little information is available regarding the role of apoptosis. In the present study, we examined the induction of apoptosis on ADR treatment and anti-apoptotic effects of probucol, a lipid-lowering drug, and we also studied the changes of bcl-2 expression in order to see the molecular mechanisms underlying the effect of probucol.
Methods
: Cardiac myocytes were isolated from 3-day-old rats, and cultured in low(1μM) or high doses(10μM) of ADR for 24 hours. Probucol(50μM) was added 30 minutes before ADR administration. Apoptosis was determined by TUNEL staining, and bcl-2 expression was estimated by immunocytochemistry.
Results
: The number of TUNEL-positive cells significantly increased in both groups treated with ADR. However, anti-apoptotic effect of probucol was evident only in low dose. In addition, the expression of bcl-2 was significantly increased only in the low-dose ADR treatment group and its expression was inhibited by pretreatment of probucol.
Conclusion
: These results suggest that apoptosis might play an important role in ADR-induced cardiotoxicity, and ADR-induced apoptosis was partially prevented by pretreatment of probucol. And ADR-induced apoptosis was not related with depression of bcl-2. Additionally, inhibition of bcl-2 gene expression of low-dose ADR treatment group by probucol suggests that another cell survival mechanism could be implicated in the action of probucol.
Key Words: Adriamycin, Apoptosis, Probucol, Bcl-2, Cardiac myocytes


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