Effects of (-)doxazosin on histomorphologic and cell apoptotic changes of the hyperplastic prostate in castrated rats.
BACKGROUND
(-)Doxazosin is one of the enantiomers of (+/-)doxazosin, and it was reported that (-)doxazosin possessed higher selectivity for lower urinary tract between the cardiovascular system and the urinary system in the animal experiments in comparison with that of (+/-)doxazosin and (+)doxazosin. Therefore, it is important to know whether (-)doxazosin has a therapeutic effect on the hyperplastic prostate.


METHODS
(-)Doxazosin and (+/-)doxazosin were administered intragastrically to prostatic hyperplasia rats, induced by testosterone propionate for 4 weeks, and each experimental group contained 8 animals. The histomorphologic changes of the prostate were observed under light microscope, the quantitative analysis of the prostatic glandular cavity was performed using an image analysis system, and the cell apoptosis was detected by using flow cytometry.


RESULTS
In comparison with model-control group, the volume index of the prostate in (-)doxazosin 3.0 mg/kg group became significantly smaller. The maximal diameter, perimeter, and area of the hyperplastic prostate glandular cavity, and the glandular epithelial cell height in (-)doxazosin (0.3, 1.0, and 3.0 mg/kg) groups and (+/-)doxazosin group were significantly reduced. (-)Doxazosin and (+/-)doxazosin did not significantly affect cell cycle distribution and cell proliferation index of the hyperplastic prostate. However, apoptotic rates of the prostatic cells in (-)doxazosin (0.3, 1.0, and 3.0 mg/kg) groups and (+/-)doxazosin group were significantly increased in comparison with those of model-control group.


CONCLUSIONS
Both (-)doxazosin and (+/-)doxazosin inhibit the prostatic hyperplasia induced by testosterone propionate in castrated rats. The induction of prostate cell apoptosis might be one of the mechanisms underlying the therapeutic role of (-)doxazosin.
Tian
He-Lin
HL
School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Zhao
Ding
D
Ren
Lei-Ming
LM
Su
Xian-Hui
XH
Kang
Yan-Hui
YH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017292:Doxazosin / Q000627:therapeutic use*; D008297:Male; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D043343:Testosterone Propionate / Q000633:toxicity
D017292:Doxazosin; D043343:Testosterone Propionate