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Related Experiment Videos

Rapidly developing cocaine-induced peripheral portal liver damage.

S J Charles1, C J Powell

  • 1DH Department of Toxicology, St Bartholomews Hospital Medical College, London, UK.

Toxicology Letters
|December 1, 1992
PubMed
Summary

Cocaine causes rapid liver damage in mice within 2 hours, indicated by cell necrosis and elevated liver enzymes. Prompt medical attention is crucial for suspected cocaine overdose.

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Area of Science:

  • Toxicology
  • Hepatology
  • Pharmacology

Background:

  • Cocaine is a potent stimulant with known cardiotoxic effects.
  • Hepatotoxicity following cocaine use is a recognized clinical concern.
  • The precise mechanisms and timeline of cocaine-induced liver injury require further elucidation.

Purpose of the Study:

  • To investigate the temporal relationship between cocaine administration and the onset of liver damage in a murine model.
  • To assess biochemical markers of liver injury and cellular integrity following cocaine exposure.
  • To examine the role of cytochrome P-450 and lipid peroxidation in cocaine-induced hepatotoxicity.

Main Methods:

  • DBA/2Ha mice were treated with phenobarbitone followed by cocaine administration.
  • Liver tissue and plasma samples were collected at 2 and 3 hours post-cocaine administration.

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  • Histopathological examination assessed peripheral portal cell necrosis and plasma membrane integrity.
  • Liver microsomes were analyzed for total cytochrome P-450 and malondialdehyde (MDA) levels.
  • Main Results:

    • Scattered peripheral portal cell necrosis was observed within 2 hours of cocaine administration.
    • Widespread hepatic lesions and compromised plasma membrane integrity were evident by 3 hours.
    • Plasma levels of liver enzymes showed a 15-fold increase at 3 hours.
    • No significant changes in total cytochrome P-450 levels or correlation between MDA and liver damage were found.

    Conclusions:

    • Cocaine induces rapid and significant liver damage in mice, manifesting as early as 2 hours post-administration.
    • The observed hepatotoxicity is not directly correlated with alterations in total cytochrome P-450 or lipid peroxidation.
    • These findings underscore the urgency of medical intervention in cases of suspected cocaine overdose due to the swift onset of liver injury.