Carnitine metabolism in rats with 4-pentenoic acid induced fatty liver.

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.