The effects of docetaxel and/or captopril in expression of TGF-β1, MMP-1, CTGF, and PAI-1 as markers of anterior urethral stricture in an animal model

Background: Treatment of urethral trauma is currently done after urethral stricture occurs. Stricture therapy after occurrence gives unsatisfactory success rates. Several genes, such as transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 1 (MMP-1), connective tissue growth factor (C...

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Veröffentlicht in:Therapeutic advances in urology 2020, Vol.12, p.1756287220927994-1756287220927994
Hauptverfasser: Kurniawan, Wikan, Soesatyo, Marsetyawan Heparis Nur Ekandaru, Aryandono, Teguh
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Sprache:eng
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Zusammenfassung:Background: Treatment of urethral trauma is currently done after urethral stricture occurs. Stricture therapy after occurrence gives unsatisfactory success rates. Several genes, such as transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 1 (MMP-1), connective tissue growth factor (CTGF), and plasminogen activator inhibitor 1 (PAI-1), have a proven role in urethral stricture development. The purpose of this study was to assess the effect docetaxel and/or captopril on the RNA expression of those genes. Methods: The subjects of this research were 26 male New Zealand rabbits aged 230 ± 20 days weighing 4–5 kg that underwent urethral rupture by endoscopic resection under anesthetized conditions. Subjects were divided into five groups; control, stricture, captopril (captopril 0.05 mg/rabbit/day), docetaxel (docetaxel 0.1 mg/rabbit/day), and docetaxel-captopril (docetaxel 0.1 mg/rabbit/day and captopril 0.05 mg/rabbit/day). Each group consisted of 4–6 rabbits. Each rabbit received a water-soluble transurethral gel containing drug according to its group for 28 days. After the treatment period, rabbits were sacrificed with 200 mg Pentothal, and the corpus spongiosum was then prepared for real-time PCR examination. Results: TGF-β1 RNA expression in the stricture group was statistically different from that in the control, docetaxel and docetaxel-captopril groups (p = 0.016; p = 0.016; p = 0.004). The stricture group did not exhibit any statistical difference from the captopril group (p = 0.190). The control group did not show any statistically difference from the captopril, docetaxel, and docetaxel-captopril groups (p = 0.114; p = 0.190; p = 1.000). Docetaxel-captopril suppresses expression of TGF-β1 RNA most significantly. MMP-1 RNA expression showed no significant differences among groups (p = 0.827). The docetaxel group and stricture group pair was most significant (p = 0.247), compared with other pairs of stricture groups in MMP-1 RNA expression. CTGF RNA expression in the stricture group was statistically different from that of control, captopril, docetaxel, and docetaxel-captopril groups (p = 0.003; p = 0.019; p = 0.005; p = 0.005). The control group did not exhibit any statistically difference from the captopril, docetaxel, and docetaxel-captopril groups (p = 0.408; p = 0.709; p = 0.695). There was no statistical difference among treatment groups. Docetaxel and docetaxel-captopril groups suppress the most significant expression of CTGF RNA exp
ISSN:1756-2872
1756-2880
DOI:10.1177/1756287220927994