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MPD - Phenotype data: acetaminophen
acetaminophen
(pain reliever e.g. Tylenol)
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blood — clinical chemistry — enzymes — ALT         metabolic panel  
Threadgill1
alanine aminotransferase (serum ALT) [IU/L]     control and  acetaminophen
      100 mg/kg:
            • control  ...... 29.0 (N=2)  
            • 4h  ...... 36.3 (N=3)  
            • 12h  ...... 96.3 (N=3)  
            • 24h  ...... 93.0 (N=3) ▲▲  
              • time comparison  
37 strains   age 8-17wks
  Inbred
Threadgill2
alanine aminotransferase (serum ALT) [IU/L]   acetaminophen   50mg/kg
      • 50 mg/kg  ...... 28.2  
      • 300 mg/kg  ...... 3101 (N=4)  
        • comparison  
5 strains   age 6-8wks
  Inbred
 
blood — clinical chemistry — enzymes — AST         metabolic panel  
Threadgill1
aspartate aminotransferase (serum AST) [IU/L]     control and  acetaminophen
      • control  ...... 108 (N=2)  
      post-Rx mg/kg:
            • 100  ...... 331 (N=3) ▲▲  
            • 200  ...... 330 (N=3)  
            • 300  ...... 166 (N=3)  
              • comparison  
37 strains   age 8-17wks
  Inbred
 
blood — clinical chemistry — urea nitrogen         metabolic panel  
Threadgill1
blood urea nitrogen (BUN) [mg/dL]     control and  acetaminophen
      • control  ...... 15.0 (N=1)  
      post-Rx mg/kg:
            • 100  ...... 14.7 (N=3)  
            • 200  ...... 21.3 (N=3)  
            • 300  ...... 17.7 (N=3)  
              • comparison  
36 strains   age 8-17wks
  Inbred
 
blood — xenobiotics — drug and metabolite concentration         HPLC  
Threadgill2
serum acetominophen (APAP) [µg/mL]     baseline and  acetaminophen 50mg/kg
      • baseline  ...... 2.66  
      • 0.5h  ...... 5.48  
      • 1h  ...... 1.96  
      • 2h  ...... 0.562  
      • 3h  ...... 0.520  
      • 6h  ...... 0.366  
        • time comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
serum acetaminophen sulfate (APAP-sulfate) [µg/mL]     baseline and  acetaminophen 50mg/kg
      • baseline  ...... 0.646  
      • 0.5h  ...... 7.05  
      • 1h  ...... 5.60  
      • 2h  ...... 2.03  
      • 3h  ...... 1.22  
      • 6h  ...... 1.25  
        • time comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
serum acetaminophen glucuronide (APAP-Glc) [µg/mL]     baseline and  acetaminophen 50mg/kg
      • baseline  ...... 2.45  
      • 0.5h  ...... 31.0  
      • 1h  ...... 16.2  
      • 2h  ...... 4.95  
      • 3h  ...... 3.26  
      • 6h  ...... 3.38 (N=4)  
        • time comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
serum acetominophen (APAP) [µg/mL]     baseline and  acetaminophen 300mg/kg
      • baseline  ...... 38.0 (N=4)  
      • 0.5h  ...... 128 (N=4)  
      • 1h  ...... 99.1 (N=4)  
      • 2h  ...... 46.3 (N=4)  
      • 3h  ...... 28.8 (N=4)  
      • 6h  ...... 13.6 (N=4)  
        • time comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
serum acetaminophen sulfate (APAP-sulfate) [µg/mL]     baseline and  acetaminophen 300mg/kg
      • baseline  ...... 2.20 (N=4)  
      • 0.5h  ...... 17.8 (N=4)  
      • 1h  ...... 25.1 (N=4)  
      • 2h  ...... 31.1 (N=4)  
      • 3h  ...... 31.1 (N=4)  
      • 6h  ...... 18.2 (N=3)  
        • time comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
serum acetaminophen glucuronide (APAP-Glc) [µg/mL]     baseline and  acetaminophen 300mg/kg
      • baseline  ...... 11.3 (N=4)  
      • 0.5h  ...... 220 (N=4)  
      • 1h  ...... 344 (N=4)  
      • 2h  ...... 270 (N=4)  
      • 3h  ...... 206 (N=4)  
      • 6h  ...... 63.8 (N=3)  
        • time comparison  
5 strains   age 6-8wks
  Inbred
 
liver — enzyme homeostasis         ELISA  
Threadgill1
cytochrome P450 1A2 isoform [pmol/mg]     control and  acetaminophen 300 mg/kg
      • control  ...... 104 (N=3)  
      • post-Rx 300 mg/kg  ...... 145 (N=3)  
        • comparison  
36 strains   age 8-12wks
  Inbred
Threadgill1
cytochrome P450 2E1 isoform [pmol/mg]     control and  acetaminophen 300 mg/kg
      • control  ...... 88.2 (N=3)  
      • post-Rx 300 mg/kg  ...... 89.7 (N=3)  
        • comparison  
36 strains   age 8-12wks
  Inbred
 
liver — enzyme homeostasis         HPLC  
Threadgill1
glutathione transferase [µg/mL]     control and  acetaminophen 300 mg/kg
      • control  ...... 537 (N=3)  
      • post-Rx 300 mg/kg  ...... 762 (N=3)  
     
36 strains   age 8-12wks
  Inbred
 
liver — enzyme homeostasis         metabolic panel  
Threadgill1
catalase [µg/mL]     control and  acetaminophen 300 mg/kg
      • control  ...... 457 (N=3)  
      • post-Rx 300 mg/kg  ...... 393 (N=3)  
        • comparison  
36 strains   age 8-12wks
  Inbred
 
liver — pathology         histopathology  
Threadgill1
necrosis [%]     control and  acetaminophen
      • control  ...... 0 (N=3)  
      post-Rx mg/kg:
            • 100  ......
            • 200  ......
            • 300  ...... 10.7 (N=3)  
              • comparison  
37 strains   age 8-17wks
  Inbred
Threadgill2
liver necrosis score   [%] ...... 45.9 (N=4)     acetaminophen   300mg/kg
5 strains   age 6-8wks
  Inbred
Threadgill2
percent nitrotyrosine staining (marker of hepatocyte injury)   [%] ...... 32.6 (N=4)     acetaminophen   300mg/kg
5 strains   age 6-8wks
  Inbred
 
liver — protein homeostasis — glutathione         HPLC  
Threadgill1
reduced glutathione (GSH) [µmol/g]     control and  acetaminophen
      • control  ...... 5.00 (N=2)  
      • post-Rx 300mg/kg  ...... 1.31 (N=4)  
        • comparison  
35 strains   age 8-17wks
  Inbred
Threadgill1
oxidized glutathione (GSSG) [µmol/g]     control and  acetaminophen
      • control  ...... 0.253 (N=2)  
      • post-Rx 300mg/kg  ...... 0.160 (N=4)  
        • comparison  
35 strains   age 8-17wks
  Inbred
Threadgill1
total glutathione (GSH plus GSSG) [µmol/g]     control and  acetaminophen
      • control  ...... 5.50 (N=2)  
      • post-Rx 300 mg/kg  ...... 1.63 (N=4)  
        • comparison  
37 strains   age 8-17wks
  Inbred
Threadgill1
ratio of reduced (GSH) to oxidized (GSSG) glutathione [ratio]     control and  acetaminophen
      • control  ...... 27.2 (N=2)  
      • post-Rx 300mg/kg  ...... 8.09 (N=4)  
        • comparison  
35 strains   age 8-17wks
  Inbred
Threadgill2
reduced glutathione (GSH) [µmol/mg]     control and  acetaminophen 300mg/kg
      • control  ...... 10.1 (N=3)  
      • post-Rx 300 mg/kg  ...... 5.08  
        • comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
percent reduced glutathione [%]     control and  acetaminophen 300mg/kg
      • control  ...... 81.2 (N=3)  
      • post-Rx 300 mg/kg  ...... 71.6  
        • comparison  
5 strains   age 6-8wks
  Inbred
Threadgill2
total glutathione [µmol/mg]     control and  acetaminophen 300mg/kg
      • control  ...... 13.5 (N=3)  
      • post-Rx 300 mg/kg  ...... 7.22  
        • comparison  
5 strains   age 6-8wks
  Inbred
 
liver — weight         scales  
Threadgill1
liver weight [g]     control and  acetaminophen
      • control  ...... 0.922  
      24h post-Rx mg/kg:
            • 100  ...... 1.23 (N=3)  
            • 200  ...... 0.867 (N=3)  
            • 300  ...... 1.00 (N=3)  
              • comparison  
37 strains   age 8-17wks
  Inbred


 


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