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Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes
Luis A Justulin1, Flavia K Delella, Sérgio L Felisbino
1Department of Cell Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
Abstract:
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.
Insights
Doxazosin (Dox) treatment in rats altered prostate structure, reducing cell proliferation and increasing apoptosis. This alpha-adrenoceptor antagonist induced significant tissue remodeling, highlighting the role of collagen fibers in the prostate.
Area of Science:
- Urology
- Pharmacology
- Cell Biology
Background:
- Doxazosin (Dox) is an alpha-adrenoceptor antagonist clinically used for benign prostatic hyperplasia (BPH).
- Understanding Dox's effects on prostate tissue structure and cellular dynamics is crucial for BPH management.
- The rat prostatic complex offers a relevant model for studying drug-induced prostatic changes.
Purpose of the Study:
- To investigate the structural and cellular effects of doxazosin on the rat prostatic complex.
- To assess changes in collagen fiber content, cell proliferation, and apoptosis following doxazosin treatment.
- To elucidate the role of tissue remodeling and collagen in doxazosin-induced prostatic alterations.
Main Methods:
- Adult Wistar rats were treated with doxazosin (25 mg/kg/day).
- Prostate tissues were analyzed at 3, 7, and 30 days post-treatment using histochemistry, morphometry-stereology, immunohistochemistry (BrdU), Western blotting (PCNA), and TUNEL assay.
- Cell proliferation and apoptosis were quantified to assess doxazosin's impact.
Main Results:
- Doxazosin treatment initially increased prostate weight and altered epithelial and smooth muscle cell morphology.
- By day 30, prostates showed a ~20% weight reduction with increased collagen and reticular fibers in the stroma.
- Doxazosin significantly reduced epithelial cell proliferation (PCNA, BrdU) and increased apoptosis (TUNEL) across prostatic lobes, with anterior and ventral regions being more affected.
Conclusions:
- Doxazosin treatment induces significant tissue remodeling in the rat prostate.
- The drug alters epithelial cell behavior, decreasing proliferation and increasing apoptosis.
- Increased collagen fiber content plays a key role in doxazosin-induced prostatic tissue remodeling.
