Threadgill2: Drug study: Acetaminophen pharmakokinetics and drug-induced liver injury in males of 5 inbred strains of mice (2005)

Harrill AH, Watkins PB, Su S, Ross PK, Harbourt DE, Stylianou IM, Boorman GA, Russo MW, Sackler RS, Harris SC, Smith PC, Tennant R, Bogue M, Paigen K, Harris C, Contractor T, Wiltshire T, Rusyn I, Threadgill DW. Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res. 2009 Sep;19(9):1507-15. Epub 2009 May 5.   PubMed 19416960     FullText

Harrill AH, Ross PK, Gatti DM, Threadgill DW, Rusyn I. Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel. Toxicol Sci. 2009 Jul;110(1):235-43. Epub 2009 May 6.   PubMed 19420014     FullText


         
An investigation of liver injury after oral administration of acetaminophen (N-acetyl-p-aminophenol; APAP) in various doses. The study involved 3 cohorts, including controls as well as animals treated with acetaminophen 50 and 300 mg/kg body weight. Animals were evaluated in these areas: blood and liver chemistry, serum drug and metabolite concentration, and liver pathology. Data are presented here for selected cohorts and measurements.

Procedures conducted:
• metabolic panel  Alanine transaminase (serum). Acetaminophen (several doses) vs. control.
• metabolite quantification  Glutathione.
• drug and metabolite quantification  Acetaminophen metabolite concentrations (serum) and liver protein homeostasis. Baseline vs. acetaminophen (several doses, several timepoints).
• histopathology  Liver histopathology, necrosis, injury after acetaminophen vs. control. 18h fast.

Threadgill2 downloads
• Download Threadgill2 project data set     animal data, as uploaded
• Download Threadgill2 animal data matrix     with factor-related expansion applied as necessary
• Download Threadgill2 strain means, SD, N, etc.     one row per strain/sex/measure
Investigators David W Threadgill       Texas A&M University,  College Station, TX
Alison Harrill       University of Arkansas for Medical Sciences,  Little Rock, AR
Participants Ross PK, Rusyn I
ContactDavid W Threadgill     dwthreadgill@tamu.edu     Lab web site
Part of a series: • Phase 1   see Threadgill1
• Phase 2   (this project) Threadgill2
AcknowledgementsFunding provided by NIH ES07126, ES11391, ES10126, GM38149, RR00046, ES35513, ES25497, ES65406; US Environmental Protection Agency STAR-RD832720

For technical assistance and histology: Balletta L, Bradford B, Lodestro C, Lee D, Maki A, Kosyk O, Woods C, Clore E, Hodges N, Boorman G. For serum enzyme testing: Kim H and the Clinical Chemistry Core Facility (UNC).
Project type Phenotype strain survey data set
MPD identifiersThreadgill2     MPD:396
Data changelog No updates/corrections.       Initial release date: 03/2012.
Formatted citation
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Mice: inbred   5 strains   ♂   age 6-8wks   3 experimental groups

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Data set
Procedure / Protocol
Treatment
Phenotype Measure / Variable (click to view)
Panel
No. of Strains
Sex
Age
Sample Size (Avg)
    Threadgill2 metabolic panel acetaminophen alanine transaminase (serum ALT)   [IU/L]  ALT   39602     50 mg/kg    300 mg/kg inbred 5 m 6-8wks N=5
    Threadgill2 histopathology acetaminophen liver necrosis score   [%]  liver_necrosis   39603 inbred 5 m 6-8wks N=5
    Threadgill2 histopathology acetaminophen percent nitrotyrosine staining (marker of hepatocyte injury)   [%]  pct_nitrotyrosine   39604 inbred 5 m 6-8wks N=5
    Threadgill2 metabolite quantification acetaminophen reduced glutathione (GSH)   [µmol/mg]  GSH   39605     control    post-Rx 300 mg/kg inbred 5 m 6-8wks N=4
    Threadgill2 metabolite quantification acetaminophen percent reduced glutathione   [%]  GSH_pct   39606     control    post-Rx 300 mg/kg inbred 5 m 6-8wks N=4
    Threadgill2 metabolite quantification acetaminophen total glutathione   [µmol/mg]  GSH_total   39607     control    post-Rx 300 mg/kg inbred 5 m 6-8wks N=4
    Threadgill2 drug and metabolite quantification acetaminophen serum acetaminophen (APAP), 50 mg/mL dose acetaminophen   [µg/mL]  APAP50   39609     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
    Threadgill2 drug and metabolite quantification acetaminophen serum acetaminophen sulfate (APAP-sulfate), 50 mg/mL dose acetaminophen   [µg/mL]  APAP_Sulf_50   39616     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
    Threadgill2 drug and metabolite quantification acetaminophen serum acetaminophen glucuronide (APAP-Glc), 50 mg/mL dose acetaminophen   [µg/mL]  APAP_Glc_50   39622     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=4
    Threadgill2 drug and metabolite quantification acetaminophen serum acetaminophen (APAP), 300 mg/mL dose acetaminophen   [µg/mL]  APAP300   39632     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
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