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Title: Indole-3-carbinol, but not its major digestive product 3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and cytochromes P450

Abstract

Indole-3-carbinol (I-3-C) and 3,3'-diindolylmethane (DIM) have been shown to reduce the incidence and multiplicity of cancers in laboratory animal models. Based on the observation that I-3-C induced hepatocyte hypertrophy when administered orally for 13 weeks to rats, a treatment and recovery study was undertaken to test the hypothesis that the induction of hepatocyte hypertrophy and cytochrome P450 (CYP) activity by I-3-C are adaptive, reversible responses. Additionally, we directly compared the effects of I-3-C to those of its principle metabolite DIM. Rats were treated orally for 28 days with 2 doses of I-3-C (5 and 50 mg I-3-C/kg body weight/day) and DIM (7.5 and 75 mg DIM/kg body weight/day) and then one-half of the animals were not treated for an additional 28 days. Organ weights, histopathology, and the CYP enzyme activities of 1A1/2, 2B1/2, 2C9, 2D6, 2E1, 3A4, and 19 A were measured both after treatment and after recovery. Oral administration of 50 mg I-3-C/kg body weight/day to rats for 28 days significantly increased liver weights and CYP enzyme activities. The effects in males were more pronounced and persistent after recovery than the effects in females. The increased organ weights returned to control values after treatment. Conversely, DIM did not altermore » liver weights and had no effect on CYP activities after the 28-day treatment. Some changes in CYP activities were measured after the DIM recovery period but the magnitudes of the changes were considered biologically insignificant. The results show that I-3-C, but not DIM, induces reversible adaptive responses in the liver.« less

Authors:
 [1];  [2];  [3];  [4];  [2]
  1. Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., MSC 7322 Bldg. EPN, Rm 2118, Bethesda, MD 20892-7322 (United States). E-mail: jc94h@nih.gov
  2. Southern Research Institute, Birmingham, AL 35205 (United States)
  3. Department of Pharmacology, University of Illinois, Chicago, IL 60612 (United States)
  4. Pathology Associates Inc., Chicago, IL 60612 (United States)
Publication Date:
OSTI Identifier:
20783435
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 211; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2005.06.011; PII: S0041-008X(05)00376-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CYTOCHROMES; ENZYME ACTIVITY; HYPERTROPHY; INDOLES; LABORATORY ANIMALS; LIVER; METHANOL; MULTIPLICITY; NEOPLASMS; RATS

Citation Formats

Crowell, James A., Page, John G., Levine, Barry S., Tomlinson, Michael J., and Hebert, Charles D. Indole-3-carbinol, but not its major digestive product 3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and cytochromes P450. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.06.011.
Crowell, James A., Page, John G., Levine, Barry S., Tomlinson, Michael J., & Hebert, Charles D. Indole-3-carbinol, but not its major digestive product 3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and cytochromes P450. United States. doi:10.1016/j.taap.2005.06.011.
Crowell, James A., Page, John G., Levine, Barry S., Tomlinson, Michael J., and Hebert, Charles D. Wed . "Indole-3-carbinol, but not its major digestive product 3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and cytochromes P450". United States. doi:10.1016/j.taap.2005.06.011.
@article{osti_20783435,
title = {Indole-3-carbinol, but not its major digestive product 3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and cytochromes P450},
author = {Crowell, James A. and Page, John G. and Levine, Barry S. and Tomlinson, Michael J. and Hebert, Charles D.},
abstractNote = {Indole-3-carbinol (I-3-C) and 3,3'-diindolylmethane (DIM) have been shown to reduce the incidence and multiplicity of cancers in laboratory animal models. Based on the observation that I-3-C induced hepatocyte hypertrophy when administered orally for 13 weeks to rats, a treatment and recovery study was undertaken to test the hypothesis that the induction of hepatocyte hypertrophy and cytochrome P450 (CYP) activity by I-3-C are adaptive, reversible responses. Additionally, we directly compared the effects of I-3-C to those of its principle metabolite DIM. Rats were treated orally for 28 days with 2 doses of I-3-C (5 and 50 mg I-3-C/kg body weight/day) and DIM (7.5 and 75 mg DIM/kg body weight/day) and then one-half of the animals were not treated for an additional 28 days. Organ weights, histopathology, and the CYP enzyme activities of 1A1/2, 2B1/2, 2C9, 2D6, 2E1, 3A4, and 19 A were measured both after treatment and after recovery. Oral administration of 50 mg I-3-C/kg body weight/day to rats for 28 days significantly increased liver weights and CYP enzyme activities. The effects in males were more pronounced and persistent after recovery than the effects in females. The increased organ weights returned to control values after treatment. Conversely, DIM did not alter liver weights and had no effect on CYP activities after the 28-day treatment. Some changes in CYP activities were measured after the DIM recovery period but the magnitudes of the changes were considered biologically insignificant. The results show that I-3-C, but not DIM, induces reversible adaptive responses in the liver.},
doi = {10.1016/j.taap.2005.06.011},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 211,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2006},
month = {Wed Mar 01 00:00:00 EST 2006}
}