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Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice.
Biopharm Drug Dispos. 2019 May; 40(5-6):188-194.BD

Abstract

Two indole compounds, indole-3-carbinol (I3C) and its acid condensation product, 3,3'-diindolymethane (DIM), have been shown to suppress the expression of flavin-containing monooxygenases (FMO) and to induce some hepatic cytochrome P450s (CYPs) in rats. In liver microsomes prepared from rats fed I3C or DIM, FMO-mediated nicotine N-oxygenation was decreased, whereas CYP-mediated nicotine metabolism to nicotine iminium and subsequently to cotinine was unchanged. Therefore, it was hypothesized that in mice DIM would also suppress nicotine N-oxygenation without affecting CYP-mediated nicotine metabolism. Liver microsomes were produced from male and female C57BL/6 J and CD1 mice fed 2500 parts per million (ppm) DIM for 14 days. In liver microsomes from DIM-fed mice, FMO-mediated nicotine N-oxygenation did not differ from the controls, but CYP-mediated nicotine metabolism was significantly increased, with results varying by sex and strain. To confirm the effects of DIM in vivo, control and DIM-fed CD1 male mice were injected subcutaneously with nicotine, and the plasma concentrations of nicotine, cotinine and nicotine-N-oxide were measured over 30 minutes. The DIM-fed mice showed greater cotinine concentrations compared with the controls 10 minutes following injection. It is concluded that the effects of DIM on nicotine metabolism in vitro and in vivo differ between mice and rats and between mouse strains, and that DIM is an effective inducer of CYP-mediated nicotine metabolism in commonly studied mouse strains.

Authors+Show Affiliations

Department of Genetics, Washington University, St Louis, MO.Masonic Cancer Center, University of Minnesota, Minneapolis, MN.Department of Anesthesiology, Duke University School of Medicine, Durham, NC.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31016737

Citation

Bloom, A Joseph, et al. "Strain-specific Altered Nicotine Metabolism in 3,3'-diindolylmethane (DIM) Exposed Mice." Biopharmaceutics & Drug Disposition, vol. 40, no. 5-6, 2019, pp. 188-194.
Bloom AJ, Upadhyaya P, Kharasch ED. Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice. Biopharm Drug Dispos. 2019;40(5-6):188-194.
Bloom, A. J., Upadhyaya, P., & Kharasch, E. D. (2019). Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice. Biopharmaceutics & Drug Disposition, 40(5-6), 188-194. https://doi.org/10.1002/bdd.2182
Bloom AJ, Upadhyaya P, Kharasch ED. Strain-specific Altered Nicotine Metabolism in 3,3'-diindolylmethane (DIM) Exposed Mice. Biopharm Drug Dispos. 2019;40(5-6):188-194. PubMed PMID: 31016737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice. AU - Bloom,A Joseph, AU - Upadhyaya,Pramod, AU - Kharasch,Evan D, Y1 - 2019/05/20/ PY - 2019/01/31/received PY - 2019/04/02/revised PY - 2019/04/08/accepted PY - 2019/4/25/pubmed PY - 2020/1/22/medline PY - 2019/4/25/entrez KW - DIM KW - IC3 KW - metabolism KW - mouse KW - nicotine SP - 188 EP - 194 JF - Biopharmaceutics & drug disposition JO - Biopharm Drug Dispos VL - 40 IS - 5-6 N2 - Two indole compounds, indole-3-carbinol (I3C) and its acid condensation product, 3,3'-diindolymethane (DIM), have been shown to suppress the expression of flavin-containing monooxygenases (FMO) and to induce some hepatic cytochrome P450s (CYPs) in rats. In liver microsomes prepared from rats fed I3C or DIM, FMO-mediated nicotine N-oxygenation was decreased, whereas CYP-mediated nicotine metabolism to nicotine iminium and subsequently to cotinine was unchanged. Therefore, it was hypothesized that in mice DIM would also suppress nicotine N-oxygenation without affecting CYP-mediated nicotine metabolism. Liver microsomes were produced from male and female C57BL/6 J and CD1 mice fed 2500 parts per million (ppm) DIM for 14 days. In liver microsomes from DIM-fed mice, FMO-mediated nicotine N-oxygenation did not differ from the controls, but CYP-mediated nicotine metabolism was significantly increased, with results varying by sex and strain. To confirm the effects of DIM in vivo, control and DIM-fed CD1 male mice were injected subcutaneously with nicotine, and the plasma concentrations of nicotine, cotinine and nicotine-N-oxide were measured over 30 minutes. The DIM-fed mice showed greater cotinine concentrations compared with the controls 10 minutes following injection. It is concluded that the effects of DIM on nicotine metabolism in vitro and in vivo differ between mice and rats and between mouse strains, and that DIM is an effective inducer of CYP-mediated nicotine metabolism in commonly studied mouse strains. SN - 1099-081X UR - https://www.unboundmedicine.com/medline/citation/31016737/Strain_specific_altered_nicotine_metabolism_in_33'_diindolylmethane__DIM__exposed_mice_ DB - PRIME DP - Unbound Medicine ER -