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Studies on Orotic Acid Fatty Liver in Rats: Factors influencing the induction of fatty liver1

D. S. R. Sarma and H. Sidransky

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Orotic acid methyl ester, a more water-soluble derivative of orotic acid, when force-fed along with diet, or when administered intraperitoneally to fed rats, induced a fatty liver, increased hepatic glycogen and increased hepatic total uridine nucleotides. Hepatic ATP levels decrease when orotic acid is added to a purified diet and fed ad libitum or by force-feeding. In force-feeding experiments when control and experimental animals are killed 14 to 16 hours after the last tubefeeding, hepatic ATP levels are equally low in both groups. Under these conditions the levels in the control animals drop to the sustained low levels in the experimental animals. Rats fed a diet containing lactose, calcium lactate and orotic acid do not develop fatty liver, yet have relatively low levels of hepatic ATP. On the other hand, there are moderately high levels of hepatic uridine nucleotides which indicate that there is no significant interference with orotic acid utilization. Based on experiments with fasted and fed animals given orotic acid or orotic acid methyl ester, diet appears to play an important role in the utilization of orotic acid and in the maintenance of elevated hepatic uridine nucleotide levels. Using the luciferin-luciferase method for assay of hepatic ATP levels, it was found that the livers of rats fed orotic acid had a stabilizing effect on the luminescence due to ATP. UDP had an inhibitory effect on the luminescence due to ATP.

1 Supported by Public Health Service Research Grants nos. AM-05908 from the National Institute of Arthritis and Metabolic Diseases, CA- 07465 from the National Cancer Institute and GM-10269 from the National Institute of General Medical Sciences.

Manuscript received 12 November 1968.




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