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  • Title: Plasma levels of a novel noncyclooxygenase-derived prostanoid (8-isoprostane) correlate with severity of liver injury in experimental alcoholic liver disease.
    Author: Nanji AA, Khwaja S, Tahan SR, Sadrzadeh SM.
    Journal: J Pharmacol Exp Ther; 1994 Jun; 269(3):1280-5. PubMed ID: 8014871.
    Abstract:
    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.
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