Early discovery in rats and humanized rodents

Do you have a compound and want a quick and cost effective in vivo evaluation?  We offer a range of preliminary in vivo capabilities as well as the ability to screen compounds in both traditional animal rodent models, such as Sprague-Dawley rats and genetically engineered models (custom services & in vivo liver gene delivery available) including “humanized” liver rodent models, which are immunodeficient animals in which the native liver has been ablated and then engrafted with human hepatocytes, which proliferate to restore the functioning liver.

In vivo technical skills at Hera

  • Blood collection from live animals:
    • Tail vein
    • Jugular vein
    • Saphenous vein
  • Urine collection
  • Traditional serum chemistry panels for clinical pathology
  • Full necropsy of all organs, including images if desired
  • Fixation or flash freezing of organs
  • Histopathology, immunohistochemistry

Study 1 (alpha-naphthyl isothiocyanate/ANIT):

  • 75mg/kg dosed IP on days 0, 1, 2 (3 doses, analysis 48 hours post-dose)
  • Blood collection via cardiac puncture for clinical pathology on day 3
  • Liver extracted, fixed, and processed for histopathology on day 3

Study 2 (CCl4):

  • 5ml/kg dosed PO on days 0, 1 (2 doses, analysis 48 hours post-dose)
  • Blood collection via cardiac puncture for clinical pathology on day 3
  • Liver extracted, fixed, and processed for histopathology on day 3

Study 3 (CCl4): to optimize hepatotoxicity levels for downstream studies:

  • 5ml/kg dosed PO on days 0, 1, 2 (3 doses, analysis <24 hours post-dose)
  • Blood collection via cardiac puncture for clinical pathology on day 3
  • Liver extracted, fixed, and processed for histopathology on day 3 (results pending)

Study 1: Clinical pathology in ANIT-treated rats

Average serum chemistry data from animals treated with vehicle control or ANIT

Study 1: Histopathology results in ANIT-treated rats

Bile duct inflammatory changes

Portal changes: bile duct epithelial hypertrophy and hyperplasia; inflammatory cell infiltration; increased mitotic activity

Study 2: Clinical pathology in CCl4-treated rats

Average serum chemistry data from animals treated with vehicle control or CCl4

Control

No significant change

CCl4-treated

Cytoplasmic vacuolation, moderate to severe

Figure 3

Cytoplasmic vacuolation, centrilobular fibrosis, mononuclear cell infiltration