Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To produce an animal model of Reye's syndrome (RS), 20 adult male Wistar rats were given 10 repeated i.p. injections of 50 mg/kg 4-pentenoic acid (PA) each separated by an 8-h interval. Then, 90 min after the tenth dose, they were given a final i.p. injection of 150 mg/kg PA. Thirteen control animals were injected with vehicle only using the same time schedule. More than half the animals in each group were fed a common diet, but the others were fasted during the terminal 10-h stage. All rats were sacrificed 30 min after the last injection. At the terminal stage, in comparison with the vehicle-injected controls, hypolipemia, hypoglycemia and high titers of serum ammonia and urea N were estimated significantly in the PA-treated rats fed throughout the whole period. Hypolipemia and hypoglycemia were more prominent in the terminally fasted group than the group fed continuously. Only in the PA-treated rats fed throughout the whole period moderate morphological signs of microvesicular fatty liver were exhibited. Ultracytochemical findings and biochemical determinations showed that the major lipids in the microvesicular fatty livers were triglycerides. Morphometric analysis revealed distinct hepatic mitochondrial swelling in the PA-treated rats. Therefore, the above treatment with PA was able to induce microvesicular fatty liver in rats with resembling RS, which were fed throughout the treatment procedure, but not in the terminally fasted rats.
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PMID:Microvesicular fatty liver in rats with resembling Reye's syndrome induced by 4-pentenoic acid. 226 Apr 72

The effects of 4-pentenoic acid, a chemical claimed to induce fatty liver morphologically similar to that seen in Reye's syndrome, on carnitine metabolism and on hepatic histology were studied. Male Wistar rats were injected with 50 mg/kg doses of 4-pentenoic acid intraperitoneally every four hours over a period of 82 hours. Control rats received a similar volume of saline instead. The animals were then sacrificed at 82 hours. Liver, serum and urine were collected and stored in dry ice. The concentrations of free, acyl-, and total (free plus acyl) carnitines determined in serum were found to be significantly decreased in the rats which had received 4-pentenoic acid, while the concentrations of acyl- and total carnitines were significantly elevated in urine. In the liver tissue, the concentrations of short chain- and medium chain-acylcarnitines tended to be elevated, but the differences were not statistically significant. These results suggest that enhanced acylation of free carnitine with metabolites of 4-pentenoic acid, and excretion of the resulting acylcarnitine into urine are likely mechanism of the 4-pentenoic acid-induced hypocarnitinemia. Liver histology revealed marked fatty change with minute fat droplets similar to those observed in Reye's syndrome, and very slight alteration in mitochondrial configuration.
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PMID:Carnitine metabolism in rats with 4-pentenoic acid induced fatty liver. 228 28

Rats treated with six to eight doses (80 mg/kg, i.p.) of 4-pentenoic acid, an inhibitor of mitochondrial fatty acid oxidation in vitro, during a 48-hr starvation period developed microvesicular fatty infiltration of the liver similar to that observed in Reye's Syndrome. Hepatic triglycerides were elevated an average of 5-fold, although considerable variability was found between individual rats. Fed rats did not develop fatty liver upon similar treatment with pentenoic acid. Liver mitochondria isolated from rats with pentenoic acid-induced fatty liver showed a persistent inhibition of fatty acid oxidation. Rates of oxidation of palmitoylcarnitine and decanoylcarnitine were decreased about 70%, while that of octanoylcarnitine was decreased 50%. Carnitine-independent oxidation of octanoate was also inhibited. Oxidation rates for substrates other than fatty acids, including glutamate, succinate, pyruvate, and alpha-ketoglutarate, were unaffected. Measurements of flavoprotein reduction in intact mitochondria indicated that neither palmitoylcarnitine nor palmitoyl CoA plus L-carnitine could elicit reduction of acyl-CoA dehydrogenase and electron transferring flavoprotein in mitochondria from rats with pentenoic acid-induced fatty liver. These results support a site of inhibition of mitochondrial beta-oxidation at the level of acyl-CoA dehydrogenase for pentenoic acid treatment in vivo, and they suggest a role for nutritional or hormonal factors in the metabolic disposition of pentenoic acid in vivo and in the development of fatty liver.
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PMID:Inhibition of mitochondrial fatty acid oxidation in pentenoic acid-induced fatty liver. A possible model for Reye's syndrome. 671 30