Document Detail

Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes.
MedLine Citation:
PMID:  18188599     Owner:  NLM     Status:  MEDLINE    
We investigated the effects of doxazosin (Dox), an alpha-adrenoceptor antagonist used clinically for the treatment of benign prostatic hyperplasia (BPH), on the rat prostatic complex by assessing structural parameters, collagen fiber content, cell proliferation, and apoptosis. Adult Wistar rats were treated with Dox (25 mg/kg per day), and the ventral (VP), dorsolateral, and anterior prostate (AP) regions of the prostate complex were excised at 3, 7, and 30 days after treatment. At 24 h before being killed, the rats were injected once with 5-bromodeoxyuridine (BrdU; thymidine analog) to label mitotically active cells. The prostates were weighed and processed for histochemistry, morphometry-stereology, immunohistochemistry for BrdU, Western blotting for proliferating cell nuclear antigen (PCNA), and the TUNEL reaction for apoptosis. Dox-treated prostate lobes at day 3 presented increased weight, an enlarged ductal lumen, low cubical epithelial cells, reduced epithelial folds, and stretched smooth muscle cells. However, at day 30, the prostates exhibited a weight reduction of approximately 20% and an increased area of collagen and reticular fibers in the stromal space. Dox also reduced epithelial cell proliferation and increased apoptosis in the three prostatic lobes. Western blotting for PCNA confirmed the reduction of cell proliferation by Dox, with the AP and VP being more affected than the dorsal prostate. Thus, Dox treatment alters epithelial cell behavior and prostatic tissue mechanical demand, inducing tissue remodeling in which collagen fibers assume a major role.
Luis A Justulin; Flavia K Delella; Sérgio L Felisbino
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-10
Journal Detail:
Title:  Cell and tissue research     Volume:  332     ISSN:  0302-766X     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-19     Completed Date:  2008-07-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  171-83     Citation Subset:  IM    
Department of Cell Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
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MeSH Terms
Apoptosis / drug effects
Body Weight / drug effects
Cell Proliferation / drug effects*
Collagen / metabolism*
Doxazosin / pharmacology*
Epithelial Cells / cytology,  drug effects
In Situ Nick-End Labeling
Organ Size / drug effects
Proliferating Cell Nuclear Antigen / metabolism
Prostate / cytology,  drug effects*,  metabolism
Rats, Wistar
Reg. No./Substance:
0/Proliferating Cell Nuclear Antigen; 74191-85-8/Doxazosin; 9007-34-5/Collagen

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