Cocaine hepatotoxicity in cultured liver slices: a species comparison

Suzanne Connors; David R. Rankin; A. Jay Gandolfi; Carlos L. Krumdieck; Lawrence J. Koep; Klaus Brendel

doi:10.1016/0300-483X(90)90018-C

Cocaine hepatotoxicity in cultured liver slices: a species comparison

Suzanne Connors, David R. Rankin, A. Jay Gandolfi, Carlos L. Krumdieck, Lawrence J. Koep, Klaus Brendel

Research output: Contribution to journal › Article › peer-review

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Abstract

Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K⁺ retention and Ca²⁺ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse ≫ induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat > pig = human.

Original language	English (US)
Pages (from-to)	171-183
Number of pages	13
Journal	Toxicology
Volume	61
Issue number	2
DOIs	https://doi.org/10.1016/0300-483X(90)90018-C
State	Published - Apr 17 1990

Keywords

Cocaine hepatotoxicity
Human liver
Liver slices
Mouse liver
Pig liver
Rabbit liver
Rat liver
Species comparison

ASJC Scopus subject areas

Toxicology

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10.1016/0300-483X(90)90018-C

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@article{1d454a3f54f44da09640517301b0b8be,

title = "Cocaine hepatotoxicity in cultured liver slices: a species comparison",

abstract = "Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K+ retention and Ca2+ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse ≫ induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat > pig = human.",

keywords = "Cocaine hepatotoxicity, Human liver, Liver slices, Mouse liver, Pig liver, Rabbit liver, Rat liver, Species comparison",

author = "Suzanne Connors and Rankin, {David R.} and Gandolfi, {A. Jay} and Krumdieck, {Carlos L.} and Koep, {Lawrence J.} and Klaus Brendel",

note = "Funding Information: This work was supportedb y NIH/GM 38290. Human tissue was obtained throught he serviceso f contractN IEHS N01-ES-55112a nd was in part from the Arizona Organ Bank, the Phoenix Tissue Bank and the SouthwestO rgan Bank, Inc. We are indebtedt o Mr. Thomas Hagan in Phoenix and Mr. LawrenceB ur-nett in Tuscon for their help in procuringt his tissue. A grant from The Upjohn Company facilitatedc ertaina spectso f this work. We thank Dr. John Philip Cropper for statisticaal nalysesa nd Mrs. Anita Finnell for experts ecretariasle r-vices.",

year = "1990",

month = apr,

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doi = "10.1016/0300-483X(90)90018-C",

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AU - Connors, Suzanne

AU - Rankin, David R.

AU - Gandolfi, A. Jay

AU - Krumdieck, Carlos L.

AU - Koep, Lawrence J.

AU - Brendel, Klaus

N1 - Funding Information: This work was supportedb y NIH/GM 38290. Human tissue was obtained throught he serviceso f contractN IEHS N01-ES-55112a nd was in part from the Arizona Organ Bank, the Phoenix Tissue Bank and the SouthwestO rgan Bank, Inc. We are indebtedt o Mr. Thomas Hagan in Phoenix and Mr. LawrenceB ur-nett in Tuscon for their help in procuringt his tissue. A grant from The Upjohn Company facilitatedc ertaina spectso f this work. We thank Dr. John Philip Cropper for statisticaal nalysesa nd Mrs. Anita Finnell for experts ecretariasle r-vices.

PY - 1990/4/17

Y1 - 1990/4/17

N2 - Studies were carried out in order to find a sensitive in vitro model with which to investigate cocaine-mediated hepatotoxicity. Precision-cut liver slices were prepared from: human, domestic pig, New Zealand white rabbit, Sprague-Dawley (S/D) rat, and two mouse strains (DBA/2Ha and ICR). The rationale for the choice of these species was that information on in vivo effects of cocaine was available in the literature. Slices were cultured for up to 6 h in the presence of 0-5 mM cocaine. Indices of toxicity consisted of K+ retention and Ca2+ uptake. Minimal effects and no clear dose-response relationships were observed. In addition to the studies with non-pretreated animals, liver slices were prepared from DBA/2Ha and ICR mice, both induced by housing on pine shavings, and phenobarbital pretreated Sprague-Dawley rats. The induced ICR mouse and rat were approximately 3 times more sensitive to cocaine-mediated hepatotoxicity. The following order of sensitivity to cocaine-mediated hepatotoxicity was established: induced rat = induced ICR mouse ≫ induced DBA/2Ha mouse = rabbit = uninduced ICR mouse = uninduced DBA/2Ha mouse = uninduced rat > pig = human.

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KW - Pig liver

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KW - Rat liver

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ER -

Cocaine hepatotoxicity in cultured liver slices: a species comparison

Abstract

Keywords

ASJC Scopus subject areas

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