Metformin abrogates the voiding dysfunction induced by prolonged methylglyoxal intake

Area of Science:

• Urology
• Metabolism
• Pharmacology

Background:

• Methylglyoxal (MGO) is a reactive carbonyl species elevated in diabetic patients.
• Metformin, an anti-hyperglycemic drug, can scavenge MGO and inhibit advanced glycation end product (AGE) formation.

Purpose of the Study:

• To investigate the potential of metformin in reversing methylglyoxal (MGO)-induced bladder dysfunction.
• To explore the mechanisms underlying MGO-induced bladder changes and metformin's therapeutic effects.

Main Methods:

• Male C57/BL6 mice were administered MGO in drinking water for 12 weeks, with metformin treatment in the final two weeks.
• Bladder function was assessed using voiding behavior assays, cystometry, and in vitro bladder contractions.
• Serum MGO and AGEs levels, bladder glyoxalase (Glo1) activity, urothelium thickness, and collagen content were measured.

Main Results:

• MGO intake increased serum MGO and AGEs, reduced bladder Glo1 expression/activity, and altered bladder structure (urothelium thickness, collagen).
• MGO-induced voiding dysfunction included increased void volume, heightened bladder pressures, and reduced voiding efficiency.
• Metformin treatment normalized MGO/AGEs levels, Glo1 activity, bladder structure, and fully restored MGO-induced voiding dysfunction.

Conclusions:

• Methylglyoxal (MGO) significantly contributes to bladder dysfunction through glycation pathways.
• Metformin effectively ameliorates MGO-induced bladder dysfunction by scavenging MGO and preventing AGE formation.
• These findings highlight metformin's therapeutic potential for MGO-related urological complications.