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


       
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Participants David W Threadgill       Texas A&M University College Station, TX
Alison Harrill       University of Arkansas for Medical Sciences Little Rock, AR
With: 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
Click above to copy-paste the entire citation for this MPD web page.
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.

Summary of procedures that were 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.
Mice: inbred   5 strains   ♂   age 6-8wks   3 cohorts

Select table page: First Prev Next Last
Data set MPD ID Procedure / Protocol Drug or Challenge Phenotype Measure Panel No. of Strains Sex Age Sample Size (Avg)
    Threadgill2 39602 metabolic panel acetaminophen alanine transaminase (serum ALT)   [IU/L]     50 mg/kg    300 mg/kg inbred 5 m 6-8wks N=5
    Threadgill2 39603 histopathology acetaminophen liver necrosis score   [%]  liver_necrosis inbred 5 m 6-8wks N=5
    Threadgill2 39604 histopathology acetaminophen percent nitrotyrosine staining (marker of hepatocyte injury)   [%]  pct_nitrotyrosine inbred 5 m 6-8wks N=5
    Threadgill2 39605 metabolite quantification acetaminophen reduced glutathione (GSH)   [µmol/mg]     control    post-Rx 300 mg/kg inbred 5 m 6-8wks N=4
    Threadgill2 39606 metabolite quantification acetaminophen percent reduced glutathione   [%]     control    post-Rx 300 mg/kg inbred 5 m 6-8wks N=4
    Threadgill2 39607 metabolite quantification acetaminophen total glutathione   [µmol/mg]     control    post-Rx 300 mg/kg inbred 5 m 6-8wks N=4
    Threadgill2 39609 drug and metabolite quantification acetaminophen serum acetaminophen (APAP)   [µg/mL]     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
    Threadgill2 39616 drug and metabolite quantification acetaminophen serum acetaminophen sulfate (APAP-sulfate)   [µg/mL]     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
    Threadgill2 39622 drug and metabolite quantification acetaminophen serum acetaminophen glucuronide (APAP-Glc)   [µg/mL]     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=4
    Threadgill2 39632 drug and metabolite quantification acetaminophen serum acetaminophen (APAP)   [µg/mL]     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
    Threadgill2 39638 drug and metabolite quantification acetaminophen serum acetaminophen sulfate (APAP-sulfate)   [µg/mL]     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
    Threadgill2 39639 drug and metabolite quantification acetaminophen serum acetaminophen glucuronide (APAP-Glc)   [µg/mL]     baseline    0.5h    1h    2h    3h    6h inbred 5 m 6-8wks N=5
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