Acetaldehyde prevents nuclear factor-kappa B activation and hepatic inflammation in ethanol-fed rats

Acetaldehyde has been proposed as one of the mediators of liver injury in alcoholic liver disease. We investigated whether increased acetaldehyde levels affected the development of alcoholic liver injury. Male Wistar rats were fed a liquid diet containing fish oil and ethanol by intragastric infusion. Sustained elevations of acetaldehyde were achieved by daily treatment with two inhibitors of aldehyde dehydrogenase (ALDH): disulfiram and benzcoprine. Pathologic changes, plasma and liver acetaldehyde, nuclear factor-kappa B (NF-κB) and I kappa B α (IκBα) protein, tumor necrosis factor-α (TNF-α) and cyclooxygenase 2 (COX-2) mRNA were evaluated. Treatment with the ALDH inhibitors led to increased acetaldehyde in liver and plasma but prevented necrosis and inflammation. Steatosis was not affected. Both inhibitors decreased activation of NF-κB and down-regulated TNF-α and COX-2 expression. Decreased activation of NF-κB was accompanied by IκBα preservation. Acetaldehyde probably inhibits NF-κB activation through IκBα preservation. Down-regulation of TNF-α and COX-2 occur secondary to inhibition of NF-κB and account for the absence of necrosis and inflammation in the ALDH inhibitor-treated groups.