Scar-Modulating Effect of Intraurethral Dexpanthenol on Urethral Healing Post Urethroplasty: An Experimental Study in Rats

Hassaan M1, Elkashef A1, Barakat N1, Awadalla A2, Hashem A1, El-Seddawy F3, Abdel-Maboud M3

Research Type

Pure and Applied Science / Translational

Abstract Category

Research Methods / Techniques

Abstract 529
On Demand Research Methods / Techniques
Scientific Open Discussion Session 35
On-Demand
Basic Science Animal Study Voiding Dysfunction Molecular Biology
1. Department of Urology, Urology and Nephrology Center, Mansoura University, Egypt, 2. Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Egypt, 3. Department of General Surgery, Faculty of Veterinary Medicine, Zagazig University, Egypt
Presenter
Links

Abstract

Hypothesis / aims of study
Urethroplasty is a complex procedure that depends on functional wound healing to be successful. Excessive inflammation and fibrosis post urethroplasty may lead to recurrent urethral stricture. Dexpanthenol (DXP) is an alcoholic form of pantothenic acid that has been used for wound healing for a long time. Therefore, we evaluated the effect of intraurethral DXP on urethral healing, inflammation and fibrosis after urethroplasty in rats.
Study design, materials and methods
Fifty-four male Sprague–Dawley rats were randomly allocated into 3 groups (18 rats each); control, urethroplasty and DXP groups. Urethroplasty was performed by creating a 0.8-cm vertical midline urethral incision with a microknife, then closing the urethra and overlying corpus spongiosum using 7-0 PDS. Saline solution 0.9% and DXP (500 mg/kg) was then applied intraurethrally once a day till sacrification to urethroplasty and DXP groups, respectively. Six rats from each group were sacrificed on the postoperative days 4, 8 and 15. Penectomy was performed and the penises were then sent for routine histopathological examination, interleukin (IL)-6, transforming growth factor (TGF)-ß1, ß-catenin, vascular endothelial growth factor (VEGF) and collagen I & III relative gene expression and assessment of malondialdehyde (MDA) and nitric oxide (NO) activity.
Results
There was significant improvement in inflammation and fibrosis scores after intraurethral DXP application for 8 and 15 days (Table 1). There was also significant up-regulation of VEGF, down-regulation of IL-6, TGF-ß1, ß-catenin and collagen I & III expression and decrease in collagen I/III ratio, after 4, 8 and 15 days of intraurethral DXP administration (table 2). DXP group showed significant reduction in MDA and NO activity on days 4, 8 and 15 (Table 1). Apart from histopathology and collagen I/III ratio, intraurethral application of DXP up to 15 days significantly provided more beneficial effects.
Interpretation of results
DXP has been suggested to have an anti-inflammatory effect by decreasing the activated neutrophil and pro-inflammatory cytokine infiltration and increasing the mitotic activity. DXP resulted in significant down-regulation of IL-6 expression, thus significantly improved inflammation. As a result, it significantly down-regulated the expression of TGF-ß1, ß-catenin and collagen I & III and decreased collagen I/III ratio, so significantly improved spongiofibrosis. DXP has also been shown to support cell proliferation via up-regulation of VEGF and protect against free radicals by inhibiting the formation of reactive oxygen species (ROS) as it decreased MDA and NO production.
Concluding message
Administration of intraurethral DXP might minimize urethral inflammation and fibrosis post urethroplasty, so it might be recommended as a promising tool to prevent urethral stricture recurrence after surgery.
Figure 1 Table 1: Effect of dexpanthenol on inflammation, spongiofibrosis and free radical activity after urethroplasty
Figure 2 Table 2: Effect of dexpanthenol on gene expression of IL-6, TGF-β1, β-catenin, VEGF and collagen type I and III after urethroplasty
Disclosures
Funding None Clinical Trial No Subjects Animal Species Rat
03/11/2024 23:02:52