Fructose-Induced Bladder Remodeling: Histopathological Evidence from an Experimental Rat Model.

Abstract

Background: High-fructose diets have been associated with metabolic and lower urinary tract abnormalities, but direct histopathological evidence and the tissue changes observed after fructose withdrawal remain incompletely characterized. This study evaluated the impact of high-fructose exposure on bladder histopathology and related urinary biochemical alterations in a rat model.

Methods: Twenty-four male Wistar rats were randomly allocated to three groups (n=8 each): control, fructose withdrawal, and continuous fructose exposure. The withdrawal group received a 60% fructose solution and fructose-rich diet for 4 weeks, followed by standard chow and tap water for 2 weeks, whereas the continuous-exposure group received fructose for 6 weeks. At week 6, a single 24-hour urine sample was collected, and bladder tissue was evaluated by blinded semiquantitative histopathological scoring. One-way ANOVA with Bonferroni-adjusted post hoc comparisons, Kruskal-Wallis testing, Jonckheere-Terpstra trend testing, and Spearman correlation were used as appropriate.

Results: Urothelial hyperplasia (p<0.001), lamina propria inflammation (p=0.025), edema (p=0.008), vascular congestion (p=0.018), smooth muscle hypertrophy (p=0.025), and total histopathological injury score (p<0.001) differed among groups, with the highest total score in the continuous-exposure group. Detrusor fibrosis (p=0.332) and calcification (p=0.592) did not differ significantly. Urinary calcium (p<0.001), oxalate (p=0.023), calcium-to-creatinine ratio (p=0.044), and citrate-to-creatinine ratio (p=0.006) also differed among groups.

Conclusion: Six weeks of high-fructose exposure was associated with inflammatory and hypertrophic bladder changes in rats. Lower injury scores after 4 weeks of exposure followed by 2 weeks of withdrawal indicate attenuation, but the unequal cumulative exposure does not establish reversibility. Functional and molecular studies with exposure-matched controls are required.