Reversible long-term toxicity of epristeride in beagle dogs

doi:10.1006/taap.1998.8579

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Reversible long-term toxicity of epristeride in beagle dogs
	Sun, ZY; Feng, J; Qi, XD; Wu, HY; Zheng, WJ; Tu, ZH
刊名	TOXICOLOGY AND APPLIED PHARMACOLOGY
	1999-01-15
卷号	154 期号:2 页码:145-152
关键词	epristeride DNA target cell toxicity cytotoxicity prostatic specific antigen (PSA) dihydrotestosterone (DHT) dogs
ISSN号	0041-008X
DOI	10.1006/taap.1998.8579
文献子类	Article
英文摘要	Epristeride (17 beta-N-t-butylcarboxamide-androst-3, 5-diene-3-carboxylic acid) is an uncompetitive inhibitor of steroid 5 alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT), and has been shown to retard the growth of hyperplastic prostates, The objective of the current investigation was to research the toxic effects of epristeride and to demonstrate its reversible. In the experiment, 18 beagle dogs (male, about 6 months old) were used and divided into six groups, with each group containing three dogs. Groups A and B were placebo-treated for 180 and 240 days, Groups C and D were treated with 10 and 100 mg/kg epristeride for 180 days, and Groups E and F were treated with 10 and 100 mg/kg epristeride for 180 days and then were placebo-treated for 60 days (total 240 days), respectively. Routine analyses were performed at the 1st, 30th, 90th, 180th, and 240th days, and the dogs were autopsied at the 180th or 240th day for systemic examination and measured for relative DNA content in single prostatic epithelial cells, Each prostate was fixed with 4% Formalin, embedded in paraffin, sectioned at 6 mu m, and immunohistochemically stained for assaying the relative content (transmittance) of prostatic specific antigen (PSA) and DHT (%) with a microspectrophotometer at 650-nm wavelength, The results were that 180 days of toxicity with epristeride (100 mg/kg) on interstitial cells of testes and DNA in prostatic epithelial cells couldn't reverse during 60 days of convalescence and that the DHT and PSA levels in the gland, the volume of the gland, glandular epithelial cell height, and acinar luminal area could reverse to normal during the same convalescence. To our knowledge this is the first study documenting the toxicity of epristeride, It is necessary to further study the molecular and clinical toxicity of epristeride. (C) 1999 Academic Press.
WOS关键词	PROSTATE-SPECIFIC ANTIGEN ; 5-ALPHA-REDUCTASE INHIBITORS ; HYPERPLASIA ; FINASTERIDE ; CANCER
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ACADEMIC PRESS INC
WOS记录号	WOS:000078621100004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274762]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Sun, ZY
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Sun, ZY,Feng, J,Qi, XD,et al. Reversible long-term toxicity of epristeride in beagle dogs[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,1999,154(2):145-152.
APA	Sun, ZY,Feng, J,Qi, XD,Wu, HY,Zheng, WJ,&Tu, ZH.(1999).Reversible long-term toxicity of epristeride in beagle dogs.TOXICOLOGY AND APPLIED PHARMACOLOGY,154(2),145-152.
MLA	Sun, ZY,et al."Reversible long-term toxicity of epristeride in beagle dogs".TOXICOLOGY AND APPLIED PHARMACOLOGY 154.2(1999):145-152.