Elsevier

Biochemical Pharmacology

Volume 30, Issue 7, 1 April 1981, Pages 777-783
Biochemical Pharmacology

Hepatic periportal necrosis induced by chronic administration of cocaine

https://doi.org/10.1016/0006-2952(81)90165-9Get rights and content

Abstract

Cocaine was administered intraperitoneally to male mice at doses of 10, 20 or 30 mg/kg daily for 5 days for periods of 1, 2 and 3 weeks. A dose- and time-dependent periportal hepatic necrosis was noted. The extent of hepatic damage varied from vacuolization of hepatocytes to frank necrosis. No drug-related deaths were noted at any of the dosages studied. The hepatic damage elicited by chronic cocaine was found to be of a transient nature. Chronic cocaine treatment elevated serum glutamicpyruvic transminase levels in a dose- and time-dependent manner. Hepatic cytochrome P450 levels were depressed significantly in the 30 mg · kg−1 · day−1 dosage group at 1, 2 and 3 weeks. Hexobarbital-induced narcosis was lengthened significantly in the 30 mg · kg−1 · day−1 group throughout the course of the study. Chronic administration of cocaine produced a hepatic necrosis that closely resembled that produced by cocaine administered to animals pretreated with stimulators of hepatic metabolism.

References (19)

  • M.A. Evans et al.

    Toxic. appl. Pharmac.

    (1978)
  • L. Shuster et al.

    Life Sci.

    (1977)
  • O.H. Lowry et al.

    J. biol. Chem.

    (1951)
  • E.A. Glende

    Biochem. Pharmac.

    (1972)
  • G.B. Frank et al.

    Br. J. Pharmac. Chemother.

    (1963)
  • J.E. Steinhaus et al.

    J. Pharmac. exp. Ther.

    (1964)
  • A.L. Tatum et al.

    J. Pharmac. exp. Ther.

    (1929)
  • W. Kalow

    J. Pharmac. exp. Ther.

    (1952)
  • F. Montesinos

    Bull. Narcot.

    (1965)
There are more references available in the full text version of this article.

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Supported by USPHS Grants GM15431 and GM00058.

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