CELLULAR AND SUBCELLULAR-LOCALIZATION OF ACETALDEHYDE-PROTEIN ADDUCTSIN LIVER BIOPSIES FROM ALCOHOLIC PATIENTS

Acetaldehyde, the first product of ethanol in hepatocytes, can react w ith protein to form acetaldehyde-protein adducts (APAs), Because it ha s been suggested that these adducts could be involved in the pathogene sis of ethanol-induced hepatic lesions and in fibrogenesis, we perform ed an ultrastructural immunohistochemical study to precisely define th e cellular and subcellular localization of APAs, A preembedding techni que of indirect immunoperoxidase was performed in liver biopsy specime ns from eight patients with alcoholic liver disease, using a specific antiserum against APAs, In all specimens, APAs were detected in the ro ugh endoplasmic reticulum, in some peroxisomes, and in the cytosol of hepatocytes, In four patients with steatofibrosis or cirrhosis, labeli ng of Ito cells was also observed, Ln these cases, the same staining p attern was observed in the cytoplasmic processes of myofibroblasts in areas of fibrogenesis, When isolated rat Ito cells were incubated in t he presence of acetaldehyde, APAs were also detected in the cytoplasm, These results show that APA formation occurs in hepatocytes at the si tes of acetaldehyde production, Detection of APAs in human and rat Ito cells strongly suggests that acetaldehyde can diffuse into Ito cells and bind to cytoplasmic proteins to form local APAs, Because Ito cells are the main effector cells of liver fibrosis, detection of APAs in t hese cells points to their possible involvement in liver fibrogenesis.