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Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices.
Food Chem Toxicol. 1999 Jun; 37(6):609-18.FC

Abstract

In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague-Dawley rats. While treatment of rat liver slices for 72 hours with 2-200 microM of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 microM DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.

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Authors+Show Affiliations

Renwick AB
BIBRA International, Carshalton, Surrey, UK.
Mistry H
No affiliation info available
Barton PT
No affiliation info available
Mallet F
No affiliation info available
Price RJ
No affiliation info available
Beamand JA
No affiliation info available
Lake BG
No affiliation info available

MeSH

Aflatoxin B1AnimalsAnticarcinogenic AgentsCarcinogenicity TestsCarcinogensCytochrome P-450 Enzyme SystemDrug InteractionsIn Vitro TechniquesIndolesLiverMaleMonocrotalineRatsRats, Sprague-DawleyXenobiotics

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10478829

Citation

Renwick, A B., et al. "Effect of some Indole Derivatives On Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 37, no. 6, 1999, pp. 609-18.
Renwick AB, Mistry H, Barton PT, et al. Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices. Food Chem Toxicol. 1999;37(6):609-18.
Renwick, A. B., Mistry, H., Barton, P. T., Mallet, F., Price, R. J., Beamand, J. A., & Lake, B. G. (1999). Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 37(6), 609-18.
Renwick AB, et al. Effect of some Indole Derivatives On Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices. Food Chem Toxicol. 1999;37(6):609-18. PubMed PMID: 10478829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices. AU - Renwick,A B, AU - Mistry,H, AU - Barton,P T, AU - Mallet,F, AU - Price,R J, AU - Beamand,J A, AU - Lake,B G, PY - 1999/9/9/pubmed PY - 1999/9/9/medline PY - 1999/9/9/entrez SP - 609 EP - 18 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 37 IS - 6 N2 - In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague-Dawley rats. While treatment of rat liver slices for 72 hours with 2-200 microM of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 microM DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity. SN - 0278-6915 UR - https://www.unboundmedicine.com/medline/citation/10478829/Effect_of_some_indole_derivatives_on_xenobiotic_metabolism_and_xenobiotic_induced_toxicity_in_cultured_rat_liver_slices_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278691599000265 DB - PRIME DP - Unbound Medicine ER -