Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients.
OBJECTIVE
Non-alcoholic steatohepatitis (NASH) is a disorder that is histologically characterized by macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and fibrosis. NASH can range from a benign condition to end-stage liver disease. The mechanisms promoting transition from steatosis to NASH appear to involve multiple cellular adaptations to the oxidative stress occurring when fatty acid metabolism is altered. We evaluated the relationship between lipid peroxidation and other oxidative stress biomarkers with changes in expression of heme oxygenase-1 (HO-1) in human hepatic steatosis ranging from simple steatosis to NASH.


METHODS
HO-1 expression, lipid peroxidation, ferritin and GSH levels were assayed from liver biopsies obtained from 60 subjects: 35 with NASH, 15 with simple steatosis and 10 controls.


RESULTS
The HO-1 expression was significantly increased in NASH patients and the increase reflected the severity of the disease. A significant correlation was observed between the increased levels of HO-1 and ferritin, and between the increased levels of HO-1 and lipid peroxidation. Moreover, NASH patients with lower levels of GSH exhibited higher expression of HO-1.


CONCLUSIONS
The induction of HO-1 is an adaptive response against oxidative damage elicited by lipid peroxidation and it may be critical in the progression of the disease.
Malaguarnera
Lucia
L
Department of Biomedical Sciences, University of Catania, Via E. De Amicis, 24, 95039 Trecastagni-Catania, Italy. lucmal@mbox.unict.it
Madeddu
Roberto
R
Palio
Elisabetta
E
Arena
Nicolò
N
Malaguarnera
Mariano
M
D000328:Adult; D000368:Aged; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005293:Ferritins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis
D008565:Membrane Proteins; D012333:RNA, Messenger; D005293:Ferritins; D007501:Iron; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D005978:Glutathione