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Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in sprague-dawley rats.
Toxicol Sci. 2003 Jul; 74(1):10-21.TS

Abstract

Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are naturally occurring dietary components found in cruciferous vegetables. In the stomach, I3C forms condensation products including DIM. I3C and DIM are marketed as dietary supplements, but little is known about the safety of long-term exposure. Rats were fed either control diet, 1 or 10x the current human dose of absorption-enhanced DIM or 5-7x the maximal recommended dose of I3C. Experimental diets were fed continuously for 3 or 12 months or 2 months followed by control diet for 1 month. Results at 3 or 12 months were similar in most respects. No significant differences between groups were found in blood chemistry. A general decrease in serum enzyme levels in male rats was observed, perhaps indicative of a protective effect. Males fed I3C exhibited higher serum levels of 25-hydroxy-vitamin D3 (25OH-D3). There were no observable differences grossly or histologically between groups, although a high number of hyaline casts were found throughout the kidneys of all animals. In both sexes total hepatic CYP levels were significantly induced by I3C, but not by either dose of DIM. Induction of CYP1A1 and CYP1A2 in liver and CYP1A1 in colon was detected for both sexes fed I3C and the high dose of DIM. CYP3A2 was induced in females fed I3C or the high dose of DIM; males were induced with I3C, but not DIM. No induction of CYP1B1 in the colon was observed in either sex. Long-term exposure to DIM produced no observable toxicity, and comparison to I3C indicates that DIM is a markedly less efficacious inducer of CYP in the rat at doses relevant to human supplementation.

Authors+Show Affiliations

Department of Environmental and Molecular Toxicology and the Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12730619

Citation

Leibelt, Dustin A., et al. "Evaluation of Chronic Dietary Exposure to Indole-3-carbinol and Absorption-enhanced 3,3'-diindolylmethane in Sprague-dawley Rats." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 74, no. 1, 2003, pp. 10-21.
Leibelt DA, Hedstrom OR, Fischer KA, et al. Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in sprague-dawley rats. Toxicol Sci. 2003;74(1):10-21.
Leibelt, D. A., Hedstrom, O. R., Fischer, K. A., Pereira, C. B., & Williams, D. E. (2003). Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in sprague-dawley rats. Toxicological Sciences : an Official Journal of the Society of Toxicology, 74(1), 10-21.
Leibelt DA, et al. Evaluation of Chronic Dietary Exposure to Indole-3-carbinol and Absorption-enhanced 3,3'-diindolylmethane in Sprague-dawley Rats. Toxicol Sci. 2003;74(1):10-21. PubMed PMID: 12730619.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in sprague-dawley rats. AU - Leibelt,Dustin A, AU - Hedstrom,Olaf R, AU - Fischer,Kay A, AU - Pereira,Clifford B, AU - Williams,David E, Y1 - 2003/05/02/ PY - 2003/5/6/pubmed PY - 2004/3/3/medline PY - 2003/5/6/entrez SP - 10 EP - 21 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol Sci VL - 74 IS - 1 N2 - Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are naturally occurring dietary components found in cruciferous vegetables. In the stomach, I3C forms condensation products including DIM. I3C and DIM are marketed as dietary supplements, but little is known about the safety of long-term exposure. Rats were fed either control diet, 1 or 10x the current human dose of absorption-enhanced DIM or 5-7x the maximal recommended dose of I3C. Experimental diets were fed continuously for 3 or 12 months or 2 months followed by control diet for 1 month. Results at 3 or 12 months were similar in most respects. No significant differences between groups were found in blood chemistry. A general decrease in serum enzyme levels in male rats was observed, perhaps indicative of a protective effect. Males fed I3C exhibited higher serum levels of 25-hydroxy-vitamin D3 (25OH-D3). There were no observable differences grossly or histologically between groups, although a high number of hyaline casts were found throughout the kidneys of all animals. In both sexes total hepatic CYP levels were significantly induced by I3C, but not by either dose of DIM. Induction of CYP1A1 and CYP1A2 in liver and CYP1A1 in colon was detected for both sexes fed I3C and the high dose of DIM. CYP3A2 was induced in females fed I3C or the high dose of DIM; males were induced with I3C, but not DIM. No induction of CYP1B1 in the colon was observed in either sex. Long-term exposure to DIM produced no observable toxicity, and comparison to I3C indicates that DIM is a markedly less efficacious inducer of CYP in the rat at doses relevant to human supplementation. SN - 1096-6080 UR - https://www.unboundmedicine.com/medline/citation/12730619/Evaluation_of_chronic_dietary_exposure_to_indole_3_carbinol_and_absorption_enhanced_33'_diindolylmethane_in_sprague_dawley_rats_ DB - PRIME DP - Unbound Medicine ER -