MECHANISMS OF ALCOHOL IMPAIRMENT OF RECOVERY FROM MECHANICALLY DENUDED AREAS MADE WITHIN CULTURED RAT HEPATOCYTES

The effect of ethanol on the ability of a denuded hepatocyte cell surf ace to recover is unknown. We therefore determined the effect of ethan ol on the rate of renewal of mechanical wounds made in near-confluent monolayers of primary cultures of rat hepatocytes. We found that ethan ol exerted a dose dependent effect to impair rat hepatocyte recovery a nd that at least 12 hours of exposure to ethanol was required to induc e this impairment. The effect of ethanol to impair recovery of denuded areas of epithelium was not seen in two established renal tubular epi thelial cell lines. Ethanol impairment of rat hepatocyte recovery coul d be blocked by an alcohol dehydrogenase inhibitor (4-methyl pyrazole) and potentiated by an inhibitor of aldehyde dehydrogenase (pargyline) . The effect of ethanol to inhibit rat hepatocyte recovery of denuded areas was not associated with any change in hepatocyte cell surface ex pression of the beta(1) integrin subunit as determined by flow cytomet ry. These results suggest that acetaldehyde is responsible for ethanol inhibition of hepatocyte recovery from mechanical injury and that thi s impairment occurs independent of cell surface expression of the beta (1) integrin subunit.