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Michael Duryee, M.S.
Geoffrey M. Thiele, Ph.D.
Alcoholic liver disease (ALD) is common consequence of excessive alcohol consumption . When the liver is damaged by the intake of alcohol, repair mechanisms are deployed, which results in fibrosis or scarring of the liver. Development of this disease is due to the byproducts of ethanol metabolism. These byproducts include acetaldehyde from the metabolism of ethanol and malondialdehyde from the breakdown of cell membranes during injury. An Aldeyra product, ADX-629, is a small molecule that acts as a reactive aldehyde species (RASP) inhibitor. ADX-629 covalently binds free aldehydes, thus diminishing excessive RASP levels. To determine the aldehyde scavenging abilities of ADX-629 in attenuating fatty liver disease, precision cut liver slices (PCLS) were exposed to varying concentrations of ADX-629 as well as 25mM of ethanol. PCLS, which provide a novel in vitro/ex vivo experimental model, were then measured for triglyceride levels and supernatants were analyzed for acetaldehyde levels. It was found that ADX-629 reduced the acetaldehyde levels released from PCLS while also decreasing triglyceride levels. ADX-629 offers promising clinical uses such as in the prevention of fatty liver formation in patients with non-alcoholic steatohepatitis and in the treatment of alcoholic patients by preventing oxidative stress caused by the breakdown of ethanol thereby, preventing ALD.
Alcoholic liver disease, Aldehydes, Inflammation, Reactive aldehyde species (RASP) inhibitors, Triglycerides
Works, Duncan; Tessin, Mariah B.S.; Duryee, Michael J. M.S.; Mikuls, Ted R. M.D.; and Thiele, Geoffrey M. Ph.D., "In vitro comparison of Ethanol Metabolism in Precision Cut Liver Slices from C57Bl/6, Balb/c, DBA/2J and 129S1/SvlmJ Mice and with the Aldeyra Product ADX-629" (2021). Posters: 2021 Summer Undergraduate Research Program. 59.