THE ASSOCIATION OF INCREASING DIETARY CONCENTRATIONS OF FISH-OIL WITHHEPATOTOXIC EFFECTS AND A HIGHER DEGREE OF AORTA ATHEROSCLEROSIS IN THE AD LIB. FED RABBIT

The long-term effects of consumption of marine long-chain n-3 polyunsa turated fatty acids (PUFA) on atherosclerosis in the rabbit were exami ned. Female Dutch rabbits were fed purified diets, containing 40 energ y% total fat, for a period of 2.5 years. To study the dose-response re lationship between fish oil intake and atherosclerosis, four diets wer e formulated with fish oil levels being 0, 1, 10 and 20 energy%. A fif th and sixth group were fed an alpha-linolenic acid-(C18:3, n-3) and l inoleic acid-(C18:2, n-6) rich diet, respectively. Every 6 weeks, bloo d samples were taken for determination of clinical chemical parameters , triacylglycerol and total cholesterol levels. Feeding 10 and 20 ener gy% fish oil containing diets, resulted in an increase of liver enzyme s (AST, ALT and ALP). Histological evaluation of the liver also reveal ed adverse effects of fish oil containing diets. Triacylglycerol blood levels were similar in all groups, and remained constant throughout t he study. Total cholesterol levels in brood was significantly lower in the animals fed a linoleic acid-rich diet, as compared with the other five groups. An n-3 long-chain PUFA concentration dependent increase in aorta plaque surface area was observed in the fish oil groups. A si gnificant positive relationship was found between the group mean score for severity of liver pathology and the aorta plaque surface area. Th ese results indicate that the long-chain n-3 polyunsaturated fatty aci ds in fish oil may be hepatotoxic to the herbivorous rabbit, which may interfere with the outcome of atherosclerosis studies. This finding n ecessitates the exclusion of liver pathology in experimental studies o n atherosclerosis in animal models. (C) 1998 Elsevier Science Ltd. All rights reserved