title: Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine.
abstract: Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007) basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038) transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038) transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and fenbendazole and known drug metabolizing genes.
authors.affiliation: Department of Animal Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC, United States of America.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Howard
authors.affiliation: Department of Animal Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC, United States of America.
authors.forename: Audrey T
authors.initials: AT
authors.lastname: O'Nan
authors.affiliation: Department of Animal Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Maltecca
authors.affiliation: Department of Population Health and Pathobiology, Center for Chemical Toxicology and Research Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Baynes
authors.affiliation: Department of Animal Science, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC, United States of America.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Ashwell
mesh_terms: D000818:Animals; D001947:Breeding; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005273:Fenbendazole / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009919:Orchiectomy; D060888:Real-Time Polymerase Chain Reaction; D034421:Sus scrofa / Q000235:genetics*
chemical_list: D005273:Fenbendazole; C014558:flunixin meglumine; D003577:Cytochrome P-450 Enzyme System; D003002:Clonixin