Abstract
In diabetics, formation of advanced glycation end (AGE) products has been closely associated with cardiovascular complications. In order to mitigate the injury caused by AGEs, it is critical to understand the influence of the AGE precursor methylglyoxal. Methylglyoxal is a glycation intermediate and it has been found to be elevated in the blood of diabetic patients. The impact of methylglyoxal on cardiac cells is not well elucidated. In this study, the effects of methylglyoxal on H9C2 myoblast cell viability were evaluated. Thereafter, methylglyoxal induced cell injury was investigated by co‐treatment of methylglyoxal with metformin, aminoguanidine hydrochloride, or pyridoxamine dihydrochloride. Cell viability was evaluated after incubation of drugs for 24 hours by measuring absorbance at 450 nm by using tetrazolium to differentiate metabolically active and inactive cells (e.g., CCK‐8 kit). We found that methylglyoxal (1200 μM) significantly reduced cell viability by 72±6% when compared to the untreated control (n=4, p<0.05). By contrast, co‐treatment of metformin (1–80 mM) significantly reduced methylglyoxal‐induced cell injury and increased cell viability to 69% – 122± 6% (n=4, p<0.05 vs. methylglyoxal) when compared to the untreated control. Similarly, aminoguanidine hydrochloride (250–1000 μM) treated cells significantly increased cell viability to 77% – 109±10% (n=4, p<0.05 vs. methylglyoxal) when compared to the untreated control. Additionally, pyridoxamine dihydrochloride (0.1–15 μM, n=4) showed dose‐dependent protection to increase cell viability. Highest pyridoxamine (15 μM) treated cells completely abolished methylglyoxal induced cell injury by increasing cell viability to 99± 4% (p<0.05 vs. methylglyoxal) when compared to the untreated control. However, when the three drugs were washed out from the medium prior to the addition of the methylglyoxal, the protective effects were lost and cell viability was reduced similarly as methylglyoxal (n=1). Administration of all three drugs alone did not affect cell viability after incubation for 24 hours. The preliminary data suggests that metformin, aminoguanidine hydrochloride, or pyridoxamine dihydrochloride, when incubated concurrently with a high concentration of methylglyoxal, protect cardiac cells from methylglyoxal‐induced cell injury. The mechanism underlying the protective effects will be further investigated.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 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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