Red blood cell antioxidant and iron status in alcoholic and nonalcoholic cirrhosis.
BACKGROUND
Iron overload has been reported in alcoholic liver cirrhosis but it remains to be established whether iron is involved in inducing oxidative damage to erythrocytes in alcoholic cirrhosis. The aim of this study was to assess oxidative damage and red cell indicators of antioxidant defences in alcoholics with mild-to-severe liver cirrhosis, taking into account the iron status.


METHODS
Twenty-nine patients with alcoholic liver cirrhosis (AC) and 27 with nonalcoholic cirrhosis (NAC) were studied. Serum lipid peroxides (LPO) were assayed by a colourimetric method. Serum-free malonyldialdehyde (MDA) was assayed by selected ion monitoring in positive chemical ionization; serum 4-hydroxy-2(E)-nonenal (4-HNE) was determined by a colorimetric method. Reduced (GSH) and oxidized glutathione (GSSG), adenine and pyridine cofactors were assayed in whole blood extracts by HPLC. Hexose-monophosphate shunt (HMPS), glycolytic pathway (EMP) and antioxidant enzyme activities were determined by standard methods. Iron status was evaluated by standard clinical chemistry and by histological grading of liver iron. Nontransferrin-bound iron (NTBI) was measured in serum by HPLC.


RESULTS
GSH progressively decreased with increasing severity of liver involvement in AC and NAC. MDA, 4-HNE and NTBI were significantly higher in AC serum. Stimulation of red cell HMPS and reducing potential, in terms of NADPH production, were more pronounced in AC.


CONCLUSIONS
These results suggest that NTBI is more important than the decrease of antioxidant defences in inducing lipid peroxidation. NTBI may play a catalytic role in free radical reactions in the presence of cellular reductants such as NADPH.
Fiorelli
Gemino
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Department of Internal Medicine, Ospedale Maggiore Policlinico IRCCS, Padiglione Granelli, University of Milan, Via F. Sforza 35, 20122 Milan, Italy. medintef@mailserver.unimi.it
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D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway / Q000502:physiology
D000447:Aldehydes; D000975:Antioxidants; D008054:Lipid Peroxides; D009243:NAD; D000249:Adenosine Monophosphate; D008315:Malondialdehyde; D009249:NADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007501:Iron; D002374:Catalase; D005978:Glutathione; C027576:4-hydroxy-2-nonenal