Plasma levels of a novel noncyclooxygenase-derived prostanoid (8-isoprostane) correlate with severity of liver injury in experimental alcoholic liver disease.
We used the intragastric feeding rat model for alcoholic liver disease to investigate the relationship between pathological severity and lipid peroxidation. Lipid peroxidation was assessed by measurement, in plasma, of a novel noncyclooxygenase-derived prostanoid (8-isoprostane). Six groups of animals fed ethanol and different dietary fats (saturated fat, corn oil and fish oil) were sacrificed at 1 month. Histological liver examination, plasma measurements of 8-isoprostane and measurements of microsomal conjugated dienes were carried out. Animals fed fish oil and ethanol developed the most severe liver injury and had the highest 8-isoprostane levels in plasma (919 +/- 112 pg/ml). These levels were significantly higher than the levels seen in the corn oil-ethanol (498 +/- 105 pg/ml) (P < 0.02) and saturated fat-ethanol (28.6 +/- 11.8 pg/ml) (P < .001) groups. Rats fed saturated fat and dextrose and corn oil and dextrose had levels of < 20 pg/ml. However rats fed fish oil and dextrose had, on average, 8-isoprostane levels about 100-fold higher than those seen in the saturated fat-dextrose and corn oil-dextrose groups. A significant correlation between pathological severity and plasma 8-isoprostane levels was seen in the fish oil (r = 0.92, P < .001) and non-fish oil-treated groups (r = 0.94, P < .001). A significant correlation also was seen between 8-isoprostane levels and liver microsomal conjugated dienes (r = 0.93, P < .001). Our results provide strong support for the hypothesis that lipid peroxidation in ethanol-fed rats contributes to pathological liver injury.
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts.
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Nanji
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Khwaja
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Tahan
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Sadrzadeh
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology*; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001095:Arachidonic Acids; D028441:F2-Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D003577:Cytochrome P-450 Enzyme System; D015237:Dinoprost