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Related Experiment Videos

Cholestatic effect of carmustine in rats.

D Hoyt1, R E Larson

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, Oregon State University, Corvallis.

The Journal of Pharmacology and Experimental Therapeutics
|April 1, 1989
PubMed
Summary

Carmustine (BCNU) causes intrahepatic cholestasis in rats by reducing bile salt-independent bile flow. This drug impairs the liver's ability to excrete certain compounds, indicating a selective toxic effect.

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Area of Science:

  • Hepatology
  • Toxicology
  • Pharmacology

Background:

  • Carmustine (BCNU) is a chemotherapy agent.
  • Intrahepatic cholestasis is a condition where bile flow from the liver is impaired.
  • The specific mechanisms of BCNU-induced cholestasis are not fully understood.

Purpose of the Study:

  • To investigate the effects of carmustine (BCNU) on bile flow and liver function in rats.
  • To characterize the mechanism of BCNU-induced intrahepatic cholestasis.

Main Methods:

  • Rats were administered a single intraperitoneal dose of carmustine (BCNU).
  • Bile flow, bile salt excretion, plasma electrolyte concentrations, and bromosulfophthalein excretion were measured.
  • Hepatic perfusion was assessed in vivo.

Main Results:

  • Carmustine (BCNU) induced intrahepatic cholestasis within 48 hours, characterized by reduced bile salt-independent bile flow.
  • Increased plasma potassium and decreased plasma sodium were observed.
  • Despite reduced bile flow, bile salt excretion remained normal due to increased biliary bile salt concentration.
  • Rats treated with BCNU showed an impaired ability to concentrate bromosulfophthalein in bile.
  • No reduction in hepatic perfusion was detected, suggesting a selective effect on xenobiotic excretion.

Conclusions:

  • Carmustine (BCNU) causes a selective impairment of bile salt-independent bile flow, leading to intrahepatic cholestasis.
  • The drug appears to selectively inhibit the hepatic excretion of organic anions like bromosulfophthalein.
  • The cholestatic effects of BCNU differ from those of alpha-naphthylisothiocyanate and estrogenic steroids.

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