Title | Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Monica L Vermillion Maier, Siddens, LK, Pennington, JM, Uesugi, SL, Tilton, SC, Vertel, EA, Anderson, KA, Tidwell, LG, Ognibene, TJ, Turteltaub, KW, Smith, JN, Williams, DE |
Journal | Toxicol Appl Pharmacol |
Volume | 460 |
Pagination | 116377 |
Date Published | 2023 Feb 01 |
ISSN | 1096-0333 |
Keywords | Benzo(a)pyrene, Carcinogens, Dietary Supplements, Humans, Toxicokinetics |
Abstract | Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [C]-benzo[a]pyrene ([C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of [C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [C]-BaP. Volunteers were dosed with [C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased T and reduced C for [C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced C values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T and the plasma AUC() for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen. |
DOI | 10.1016/j.taap.2023.116377 |
Alternate Journal | Toxicol Appl Pharmacol |
PubMed ID | 36642108 |
PubMed Central ID | PMC9946811 |
Grant List | R01 ES028600 / ES / NIEHS NIH HHS / United States P30 ES030287 / ES / NIEHS NIH HHS / United States R24 GM137748 / GM / NIGMS NIH HHS / United States P42 ES016465 / ES / NIEHS NIH HHS / United States T32 ES007060 / ES / NIEHS NIH HHS / United States |