Methylglyoxal is a highly reactive α-oxoaldehyde that arises as a byproduct of glycolysis, lipid metabolism, and amino acid metabolism. Methylglyoxal reacts with protein, lipids and DNA to form advanced glycation end-products (AGEs) that play a role in diabetes pathology. Increased levels of glucose in diabetics leads to increased levels of methylglyoxal which could potentially play a role in the elevated rates of certain types of cancer in diabetes patients. Metformin is a cheap and commonly prescribed drug for diabetics and a mounting body of evidence has shown it to lower the relative risk for a variety of cancers in metformin users relative to non-diabetic individuals. The biguanide pharmacophore of metformin and other guanides have been found to react with methylglyoxal forming an imidazolinone ring. My work is focused on investigating metformin’s ability to scavenge methylglyoxal resulting in diminished protein and DNA-AGEs and decreased mutations. Methylglyoxal has been prepared from pyruvic dimethylacetal through an acid-catalyzed reflux reaction. The synthesis was optimized through fractional distillation and two of five fractions contained pure methylglyoxal as determined and quantified using 1H-NMR analysis. The reaction between methylglyoxal and metformin has been investigated by incubating both synthesized and commercially purchased methylglyoxal with metformin and analyzed via semi-quantitative HPLC. In both the synthesized and commercially purchased methylglyoxal reactions, the quantity of metformin decreases by approximately 50% in the presence of methylglyoxal. Metformin’s effect on free methylglyoxal concentration has also been investigated using a methylglyoxal 96-well plate assay. Equimolar concentrations of metformin and methylglyoxal lead to a 72% decrease in methylglyoxal concentration by the fourth day. We are in the process of using an enzyme-linked immunosorbent assay (ELISA) to quantify metformin’s effect on the protein AGE, carboxyethyl lysine and will also use LC/MS/MS to quantify the effect of metformin on the DNA-AGE, N2-(1-carboxyethyl)-2’-deoxyguanonsine (CEdG). In addition, the intestinal epithelial cell line, Caco-2, are being grown with and without metformin at physiologically relevant concentration in the media. Glyoxalase 1 inhibitor and free methylglyoxal will be utilized to investigate any protective effect that metformin may afford with respect to methylglyoxal induced cytotoxicity.

Investigating the ability of metformin to scavenge for methylglyoxal and impact downstream biological effects

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.