Severe inflammation at the anastomotic site is associated with mitochondrial dysfunction following colocystoplasty in rats.

Abstract

PURPOSE: In a rat model of colocystoplasty, we aimed to characterize mitochondrial morphological and functional alterations in neobladder tissue, with a focus on the anastomotic bladder region where prolonged severe inflammation may occur. METHODS: Male Lewis rats (8-10 weeks old) underwent colocystoplasty, with neobladder tissues sampled within 5 mm of the anastomosis excluding the colon (A-part) or from the distal bladder (B-part) at 2 and 12 weeks. Sham-operated rats (bladder incision and closure) and intact controls were included (n = 5 each). Analyses included quantitative real-time polymerase chain reaction, hematoxylin and eosin staining, immunofluorescence, transmission electron microscopy, and MitoSOX assays to evaluate inflammation, mitochondrial morphology and function, and oxidative stress. RESULTS: Compared to the B-part, sham, and control, the A-part exhibited urothelial hyperplasia, marked inflammatory cell infiltration, and upregulated interleukin (IL)-1β and IL-6. Mitochondria in the A-part were swollen and contained inclusion bodies, accompanied by upregulated growth differentiation factor 15 and downregulated heat shock protein 60, indicating impaired viability. Superoxide production was increased, while mitochondrial transcription factor A and peroxisome proliferator-activated receptor gamma coactivator 1-α were less activated in the A-part. CONCLUSION: These findings demonstrate that colocystoplasty induces persistent oxidative stress and mitochondrial dysfunction at the anastomotic site, associated with chronic inflammation.