title: Antagonistic effect of nucleic acid precursors on the anticoccidial activity of 6-azauracil.
abstract: The antagonistic phenomena to anticoccidial activities of 6-azauracil (AzU) induced by certain nucleic acid precursors were examined in battery experiments. Each nucleic acid precursor, orotate, orotidine, uracil, uridine, adenine and adenosine was mixed in feed in combination with effective levels of AzU. The test feed was provided through the test term to White Leghorn cockerels which were infected with Eimeria tenella, E. necatrix or E. acervulina. In vitro tests were also conducted for antagonistic phenomena similarly to in vivo test using E. tenella cultured in chick kidney (CK) cells. Orotate and uridine reduced dose-dependently the anticoccidial activity of AzU in E. tenella infection in chickens. Uracil and orotidine revealed similar effect. Adenine and adenosine did not show any antagonistic effect to AzU. In E. necatrix infection, orotate and uridine had a similar tendency to that of E. tenella, whereas uracil and orotidine was less pronounced. The activity of AzU against E. acervulina was also blocked by the treatment with uridine and orotate. AzU inhibited the schizont's development of E. tenella in the CK cells, and this effect was reduced by uridine, but not by orotate and orotidine. The antagonistic effect of the pyrimidine nucleic acid precursors on AzU activity suggested that the anticoccidial effect of AzU to E. tenella, E. necatrix and E. acervulina is derived from inhibition of the metabolism of pyrimidine nucleotide synthesis in these parasites.
authors.affiliation: Animal Health Research Laboratories, Takeda Chemical Industries Ltd., Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Hariguchi
authors.forename: T
authors.initials: T
authors.lastname: Okamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Matsuno
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000494:pharmacology; D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002645:Chickens / Q000469:parasitology*; D003048:Coccidiosis / Q000188:drug therapy / Q000662:veterinary*; D003049:Coccidiostats / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004351:Drug Resistance; D004539:Eimeria / Q000187:drug effects*; D005527:Food, Fortified; D008297:Male; D009694:Nucleic Acid Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D009963:Orotic Acid / Q000008:administration & dosage / Q000494:pharmacology; D011201:Poultry Diseases / Q000188:drug therapy*; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D003049:Coccidiostats; D009694:Nucleic Acid Precursors; D014498:Uracil; D009963:Orotic Acid; C008714:orotidine; C100248:azauracil; D000225:Adenine; D000241:Adenosine; D014529:Uridine