Lipid peroxidation and hepatic antioxidants in alcoholic liver disease.
The generation of hepatic liver peroxidation by free radicals has been proposed as a mechanism for ethanol induced hepatotoxicity. To investigate this hypothesis, lipid extracts from hepatic needle biopsy specimens from alcoholic subjects were examined for evidence of lipid peroxidation by measuring total conjugated dienes by derivative spectroscopy and, after hydrolysis of hepatic lipid extract and reverse phase high performance liquid chromatography, the molar ratio between a diene-conjugated linoleic acid isomer (18:2 (9,11)) and the parent linoleic acid isomer (18:2(9,12)). Changes were related to hepatic histology, iron deposition, glutathione and vitamin E values. Derivative spectroscopy minima suggestive of diene conjugation were identified at 233 and 242 nm and correlated weakly, suggesting these two minima may represent different classes of lipid dienes. There was a weak relation with inflammatory histological changes in the biopsy specimen but no correlation with hepatic iron grade, glutathione, or vitamin E lipid ratio. The proportion of 18:2(9,11) linoleic acid in hepatic lipids correlated significantly with inflammatory histological features and inversely with hepatic glutathione. Furthermore, hepatic glutathione was lower in biopsy specimens with greater iron staining. The ratio of vitamin E to lipid was not related to histological group, inflammation, or iron grade. These findings suggest that excess alcohol consumption leads to hepatic inflammation and lipid peroxidation.
Situnayake
R D
RD
Clinical Investigation Unit, Dudley Road Hospital, Birmingham.
Crump
B J
BJ
Thurnham
D I
DI
Davies
J A
JA
Gearty
J
J
Davis
M
M
D000975:Antioxidants / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology; D013057:Spectrum Analysis; D014810:Vitamin E / Q000032:analysis
D000975:Antioxidants; D014810:Vitamin E; D005978:Glutathione