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Logo of bmcurolBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Urology
 
BMC Urol. 2012; 12: 1.
Published online Jan 4, 2012. doi:  10.1186/1471-2490-12-1
PMCID: PMC3265407
Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type a injection
Tiago Gorgal,1,2 Ana Charrua,1,2,3,4 João F Silva,1,2,5 António Avelino,2,3 Paulo Dinis,1,2,5 and Francisco Cruzcorresponding author1,2,5
1Department of Urology, Hospital de São João, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
2Institute for Molecular and Cell Biology (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto - Portugal
3Department of Experimental Biology, Faculty of Medicine-University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
4Faculty of Nutrition and Food Sciences, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
5Faculty of Medicine-University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto- Portugal
corresponding authorCorresponding author.
Tiago Gorgal: tgorgal/at/sapo.pt; Ana Charrua: anacharr/at/gmail.com; João F Silva: jfalturas/at/gmail.com; António Avelino: aavelino/at/med.up.pt; Paulo Dinis: paulodinisoliveira/at/gmail.com; Francisco Cruz: cruzfjmr/at/med.up.pt
Received October 3, 2011; Accepted January 4, 2012.
Abstract
Background
Onabotulinumtoxin A (OnabotA) injection has been investigated as a novel treatment for benign prostatic enlargement caused by benign prostatic hyperplasia. An OnabotA - induced volume reduction caused by sympathetic fibers impairment has been proposed as a potential mechanism of action. Our aim was to investigate the expression of apoptosis-regulating proteins in the rat prostate following OnabotA intraprostatic injection.
Methods
Adult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group.
Results
Saline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals.
Conclusions
These results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.
Keywords: Botulinum toxin, prostate, apoptosis
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