Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction

Area of Science:

• Urology
• Pharmacology
• Cell Biology

Background:

• Bladder outlet obstruction (BOO) significantly alters bladder morphology and function.
• Understanding the molecular mechanisms underlying BOO is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the effects of metformin on bladder inflammation, fibrosis, and dysfunction in a rat model of partial BOO (pBOO).
• To elucidate the molecular pathways targeted by metformin in the context of pBOO.

Main Methods:

• A rat model of partial bladder outlet obstruction (pBOO) was established.
• Rats were treated with metformin, and bladder tissues were analyzed in early (2 wk) and chronic (9 wk) phases post-pBOO.
• Key pathways including NLR family pyrin domain containing 3 inflammasome, Smad3 signaling, and autophagy were assessed.
• Primary urothelial cells and fibroblasts were used to study metformin's cellular effects.

Main Results:

• Metformin reduced early-phase inflammation and inhibited the NLR family pyrin domain containing 3 inflammasome pathway.
• Long-term metformin treatment ameliorated bladder fibrosis, improved bladder compliance, suppressed Smad3 activation, and compensated for diminished autophagy.
• Metformin's antifibrotic effects on fibroblasts were dependent on AMP-activated protein kinase and light chain 3B.

Conclusions:

• Metformin administration alleviates inflammation in the early phase of pBOO.
• Long-term metformin treatment prevents functional and histological changes in pBOO rat bladders.
• Metformin shows potential as a therapeutic agent to inhibit bladder remodeling and alleviate bladder dysfunction secondary to BOO.