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Animal model for liver dysfunction using lomustine in Wistar rats.

B P Tiwari1, P Ramanathan, R B Patel

  • 1Radiation Medicine Center (BARC), Tata Memorial Center (TMC), Annexe. rmc@rmc.ernet.in

Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology
|February 5, 2000
PubMed
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This study developed an intrahepatic cholestasis rat model using lomustine (CCNU). This model is valuable for evaluating new hepatobiliary radiopharmaceuticals.

Area of Science:

  • Hepatology
  • Toxicology
  • Pharmacology

Background:

  • Intrahepatic cholestasis is a critical condition affecting liver function.
  • Developing reliable animal models is essential for studying cholestasis and testing therapeutic agents.

Purpose of the Study:

  • To establish an animal model of intrahepatic cholestasis using lomustine (CCNU).
  • To investigate the dose-dependent effects of CCNU on liver function and histology in rats.
  • To validate the utility of this CCNU-induced cholestasis model for preclinical research.

Main Methods:

  • Rats were administered varying doses of CCNU (10, 20, and 30 mg/Kg) via intraperitoneal injection.
  • Serum liver enzymes (bilirubin, AST, ALT, alkaline phosphatase) were monitored over time.
  • Histopathological examination of liver tissues was performed at different time points post-injection.

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Main Results:

  • CCNU administration led to dose-dependent increases in serum bilirubin, AST, ALT, and alkaline phosphatase.
  • Higher doses of CCNU (20 and 30 mg/Kg) induced significant cholestatic effects and pathological changes.
  • Histopathology revealed progressive liver damage, including inflammation, bile duct proliferation, fibrosis, and ultimately cirrhosis at 75 days with the 30 mg/Kg dose.

Conclusions:

  • Lomustine (CCNU) effectively induces intrahepatic cholestasis in a dose-dependent manner in rats.
  • The developed CCNU-induced cholestasis model exhibits progressive liver damage, mimicking human cholestatic conditions.
  • This validated animal model serves as a valuable tool for assessing the efficacy of novel hepatobiliary radiopharmaceuticals.