Metformin abrogates the voiding dysfunction induced by prolonged methylglyoxal intake

Author(s)

Oliveira, Akila L. ^[1] ; de Oliveira, Mariana G. ^[1] ; Medeiros, Matheus L. ^[1] ; Monica, Fabiola Z. ^[1] ; Antunes, Edson ^[1]

Affiliation

^[1] Univ Estadual Campinas, Dept Pharmacol, Campinas, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 910, NOV 5 2021.
• Web of Science Citations: 0

Abstract

Methylglyoxal (MGO) is a reactive carbonyl species found at high levels in blood of diabetic patients. The anti hyperglycemic drug metformin can scavenger MGO and reduce the formation of advanced glycation end products (AGEs). Here, we aimed to investigate if MGO-induced bladder dysfunction can be reversed by metformin. Male C57/BL6 mice received 0.5% MGO in drinking water for 12 weeks, and metformin (300 mg/kg, daily gavage) was given in the last two weeks. The bladder functions were evaluated by performing voiding behavior assays, cystometry and in vitro bladder contractions. MGO intake markedly elevated the levels of MGO and fluorescent AGEs in serum and reduced the mRNA expression and activity of glyoxalase (Glo1) in bladder tissues. Glucose levels were unaffected among groups. MGO intake also increased the urothelium thickness and collagen content of the bladder. Void spot assays in conscious mice revealed an increased void volume in MGO group. The cystometric assays in anesthetized mice revealed increases of basal pressure, non-voiding contractions frequency, bladder capacity, inter-micturition pressure and residual volume, which were accompanied by reduced voiding efficiency in MGO group. In vitro bladder contractions to carbachol, alpha,beta-methylene ATP and electrical-field stimulation were significantly greater in MGO group. Metformin normalized the changes of MGO and AGEs levels, Glo1 expression and activity, urothelium thickness and collagen content. The MGO-induced voiding dysfunction were all restored by metformin treatment. Our findings strongly suggest that the amelioration of MGO-induced voiding dysfunction by metformin relies on its ability to scavenger MGO, preventing its accumulation in blood. (AU)

• FAPESP's process: 18/09765-3 - Voiding and prostatic dysfunction in middle-aged rats and obese mice: focus on NADPH oxidase (NOX)
• Grantee: Mariana Gonçalves de Oliveira Taranto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
• Grantee: Edson Antunes
• Support Opportunities: Research Projects - Thematic Grants