Threadgill1: Drug study: Toxicogenetic survey of susceptibility to acetaminophen-induced liver injury in males of 37 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 administration of acetaminophen (N-acetyl-p-aminophenol; APAP) in various doses. The study involved 8 cohorts, including controls as well as animals treated with acetaminophen 30, 100, 200, 300, 600, 900, and 1200 mg/kg body weight. Animals were evaluated in these areas: blood and liver chemistry, liver function, and alterations in liver morphology. Data are presented here for selected cohorts and measurements.

Procedures conducted:
• metabolic panel  Blood urea nitrogen, alanine transaminase, aspartate transaminase (serum), liver enzyme homeostasis. Acetaminophen (several doses) vs. control, several timepoints post-Rx. 18h fast.
• histopathology  Liver histopathology, necrosis after acetaminophen vs. control. 18h fast.
• metabolite quantification  Liver protein homeostasis. Acetaminophen vs. control. 18h fast.
• biomarker quantification  Liver cytochrome isoforms. Acetaminophen vs. control. 18h fast.
• organ weights  Liver weight after acetaminophen (several doses) vs. control. 18h fast.

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Investigators David W Threadgill       Texas A&M University,  College Station, TX
Alison Harrill       University of Arkansas for Medical Sciences,  Little Rock, AR
Ivan Rusyn       Texas A&M University,  College Station, TX
Participants Ross PK
ContactDavid W Threadgill     dwthreadgill@tamu.edu     Lab web site
Part of a series: • Phase 1   (this project) Threadgill1
• Phase 2   see 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 identifiersThreadgill1     MPD:194
Data changelog 1 update/correction.       Initial release date: 02/2009.
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Mice: inbred w/CC7   37 strains   ♂   age 8-17wks   8 experimental groups

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    Threadgill1 organ weights acetaminophen liver weight 24h after treatment   [g]  liverwt   19401     dose (mg/kg): control    100    200    300 inbred w/CC7 37 m 8-17wks N=4
    Threadgill1 histopathology acetaminophen necrosis   [%]  liver_necrosis   19404     dose (mg/kg): control    100    200    300 inbred w/CC7 37 m 8-17wks N=2
    Threadgill1 metabolic panel acetaminophen alanine transaminase (serum ALT)   [IU/L]  ALT_ctrl   19406 inbred w/CC7 37 m 8-17wks N=2
    Threadgill1 metabolic panel acetaminophen alanine transaminase (serum ALT), t=4h   [IU/L]  ALT_Rx100_4h   19407 inbred w/CC7 7 m 8-17wks N=4
    Threadgill1 metabolic panel acetaminophen alanine transaminase (serum ALT), t=12h   [IU/L]  ALT_Rx100_12h   19408 inbred w/CC7 7 m 8-17wks N=4
    Threadgill1 metabolic panel acetaminophen alanine transaminase (serum ALT), t=24h   [IU/L]  ALT_Rx100_24h   19409 inbred w/CC7 7 m 8-17wks N=3
    Threadgill1 metabolic panel acetaminophen aspartate transaminase (serum AST)   [IU/L]  AST   19410     dose (mg/kg): control    100    200    300 inbred w/CC7 37 m 8-17wks N=2
    Threadgill1 metabolic panel acetaminophen blood urea nitrogen (serum BUN)   [mg/dL]  BUN   19412     dose (mg/kg) control    100    200    300 inbred w/CC7 37 m 8-17wks N=2
    Threadgill1 metabolite quantification acetaminophen reduced glutathione (GSH)   [µmol/g]  GSH   19414     control    post-Rx 300mg/kg inbred w/CC7 36 m 8-17wks N=2
    Threadgill1 metabolite quantification acetaminophen oxidized glutathione (GSSG)   [µmol/g]  GSSG   19416     control    post-Rx 300mg/kg inbred w/CC7 36 m 8-17wks N=2
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