The Effects of Metformin on Methylglyoxal‐induced cardiomyocytes cell damage

Abstract

Methylglyoxal is a precursor of advanced glycation end products which is closely related to vascular complication in diabetes. However, the direct effects of methylglyoxal on cardiac myocytes still need to be elucidated. This study investigated the dose‐dependent effects of methylglyoxal on H9C2 myoblastic cell. Furthermore, we determined if metformin would reduce methylglyoxal caused cell damage. Cell viability was evaluated by a cell counting kit‐8 assay and intracellular reactive oxygen species (ROS) was evaluated via a dichlorofluorescin diacetate (DCFDA) assay. After incubation of different doses of methylglyoxal (5 μM‐1400 μM, n=12–18) for 24 hours, lower dose range of methylglyoxal (5 μM‐800 μM) slightly increased the cell viability by 15±4% compared to the control (n=12). By contrast, higher dose methylglyoxal (1000 μM, 1200 μM, 1400 μM) significantly reduced cell viability to 74 ± 6%, 63 ± 5%, and 56 ± 7%, respectively (all p<0.05) compared to control cells. Meanwhile, higher dose of methylglyoxal (1000 μM, 1200 μM, 1400 μM) also increased intracellular ROS by 42 ± 27% (n=4), 89 ± 23% (n=4, p<0.05), and 109 ± 11% (n=3, p<0.05), respectively. By contrast, administration of metformin (1–40 mM) with methylglyoxal (1200 μM) (n=4) dose‐dependently increased cell viability. Metformin (40 mM) increased cell viability by 123± 41% (p<0.05) and reduced intracellular ROS by 70% (n=1) when compared to methylglyoxal treated cells. The preliminary data suggests that higher dose of methylglyoxal causes cardiac cells damage possibly by increased oxidative stress. Metformin can reduce oxidative stress and protect cardiac cells under higher methylglyoxal concentration and may reduce vascular complications in diabetic patients.Support or Funding InformationThis study was supported by the Center for Chronic Disorders of Aging, the Division of Research and the Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.