The impact of swim bladder on urethral stricture in animal study: the study of changes in matrix metalloproteinase-1 and transforming growth factor-beta

Abstract

Urethral stricture (US) is characterized by narrowing of the urethral lumen due to scar formation involving the epithelium and the corpus spongiosum. Effective antifibrotic therapies remain limited. This study hypothesizes that swim bladder extract may promote urethral wound healing and prevent stricture formation, assessed by evaluating Matrix Metalloproteinase-1 (MMP-1), Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), MMP-1/TIMP-1 ratio, and Transforming Growth Factor-beta (TGF-β) expression. The procedure used and the care of animals were approved by the Animal Ethics Committee in School of Veterinary Medicine and Biomedical Sciences, IPB University. An in vivo experimental design was used involving adult male New Zealand rabbits, divided into three groups: (1) urethral stricture model group, (2) 2% swim bladder gel-treated group, and (3) 5% swim bladder gel-treated group. Three rabbits from each group were euthanized at weeks 2, 4, 8, and 12. Histological and immunohistochemical (IHC) analyses including Hematoxylin and Eosin (H&E) staining, Masson trichrome staining, and assessment of MMP-1, TIMP-1, and TGF-β expression were performed. Total collagen, MMP-1, TIMP-1, and TGF-β levels were quantified using ImageJ 1.46q software. Rabbits treated with swim bladder extract demonstrated improved urethral wound healing, characterized by lower total collagen percentages, higher MMP-1 levels, lower TIMP-1 levels, higher MMP-1/TIMP-1 ratios, and reduced TGF-β expression. The 5% swim bladder gel-treated group showed greater improvement. Swim bladder extract administration in an artificial urethral stricture model may have the potential to enhance urethral wound healing by increasing MMP-1 expression and decreasing TIMP-1 and TGF-β levels, thereby reducing collagen deposition and potentially preventing fibrosis. Although the observational data suggest better outcomes, they are not statistically supported.