Hepatocyte proliferation and apoptosis in relation to oxidative damage in alcohol-related liver disease.
In alcohol-related liver disease, free radicals play a part in the pathogenesis of liver damage and may influence cell turnover. The aims of this study were to correlate lipid peroxidation, antioxidant defence and iron metabolism with cell proliferation and apoptosis in alcoholic liver injury, and also in comparison with virus-related liver disease. In 45 patients [10 with chronic alcoholic liver damage (CALD), 24 with HCV-related (HCV) and 11 with HBV-related chronic hepatitis (HBV)], and 10 control subjects, we investigated serum ferritin, liver tissue iron, cysteine, reduced/oxidized glutathione, malondialdehyde, histology with hepatocyte proliferation and the apoptotic index. Ferritin, iron levels and malondialdehyde were significantly higher in HCV and CALD than in HBV, and malondialdehyde correlated with both iron and ferritin. Glutathione levels were significantly lower in CALD than in HCV, HBV and control subjects, whereas cysteine levels were significantly higher. The apoptotic index was slightly lower in CALD, with apoptosis occurring more frequently in the centrilobular area, while CALD had fewer proliferating hepatocytes, both overall and in the periportal and centrilobular areas. This study confirms that chronic alcohol intake: (1) induces more peroxidative damage, which correlates with iron loading; (2) reduces antioxidant defence, lowering reduced glutathione liver availability; (3) induces an accumulation of cysteine, a glutathione precursor/metabolite in the liver, probably due to gamma-glutamyltransferase induction; (4) correlates with a lesser extent and different distribution of hepatocyte proliferation and apoptosis than in viral liver damage. This last finding may explain the different types of liver cirrhosis deriving from alcoholic liver damage and the lower cancer risk.
Cardin
Romilda
R
Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Sezione di Gastroenterologia, Università di Padova, Via Giustiniani 2, 35128 Padua, Italy.
D'Errico
Antonia
A
Fiorentino
Michelangelo
M
Cecchetto
Attilio
A
Naccarato
Remo
R
Farinati
Fabio
F
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002455:Cell Division; D003545:Cysteine / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D019694:Hepatitis B, Chronic / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects
D008315:Malondialdehyde; D007501:Iron; D005978:Glutathione; D003545:Cysteine