Matches in Ghent University Academic Bibliography for { <https://biblio.ugent.be/publication/01GPK9PZA2CDWAMX99KBCE81G1> ?p ?o. }
Showing items 1 to 23 of
23
with 100 items per page.
- 01GPK9PZA2CDWAMX99KBCE81G1 classification A1.
- 01GPK9PZA2CDWAMX99KBCE81G1 date "2022".
- 01GPK9PZA2CDWAMX99KBCE81G1 language "eng".
- 01GPK9PZA2CDWAMX99KBCE81G1 type journalArticle.
- 01GPK9PZA2CDWAMX99KBCE81G1 hasPart 01GPKB65PM4FJBZWW42T6KTC71.pdf.
- 01GPK9PZA2CDWAMX99KBCE81G1 subject "Biology and Life Sciences".
- 01GPK9PZA2CDWAMX99KBCE81G1 doi "10.3389/fmicb.2022.988083".
- 01GPK9PZA2CDWAMX99KBCE81G1 issn "1664-302X".
- 01GPK9PZA2CDWAMX99KBCE81G1 volume "13".
- 01GPK9PZA2CDWAMX99KBCE81G1 abstract "Mycotoxins, fungal secondary metabolites, are ubiquitously present in food commodities. Acute exposure to high levels or chronic exposure to low levels has an impact on the human body. The phase I metabolism in the human liver, performed by cytochrome P450 (CYP450) enzymes, is accountable for more than 80% of the overall metabolism of exogenous and endogenous compounds. Mycotoxins are (partially) metabolized by CYP450 enzymes. In this study, in vitro research was performed on CYP450 probes and aflatoxin B1 (AFB1), a carcinogenic mycotoxin, to obtain pharmacokinetic data on AFB1, required for further experimental work. The CYP450 probes of choice were a CYP3A4 substrate, midazolam (MDZ) and a CYP1A2 substrate, phenacetin (PH) since these are the main metabolizing phase I enzymes of AFB1. Linearity experiments were performed on the three substrates indicating that linear conditions were achieved at a microsomal protein concentration and incubation time of 0.25 mg/ml and 5 min, 0.50 mg/ml and 20 min and 0.25 mg/ml and 5 min for MDZ, PH and AFB1, respectively. The K-m was determined in human liver microsomes and was estimated at 2.15 mu M for MDZ, 40.0 mu M for PH and 40.9 mu M for AFB1. The associated V-max values were 956 pmol/(mg.min) (MDZ), 856 pmol/(mg.min) (PH) and 11,536 pmol/(mg.min) (AFB1). Recombinant CYP systems were used to determine CYP450-specific Michaelis-Menten values for AFB1, leading to a CYP3A4 K-m of 49.6 mu M and an intersystem extrapolation factor (ISEF) corrected V-max of 43.6 pmol/min/pmol P450 and a CYP1A2 K-m of 58.2 mu M and an ISEF corrected V-max of 283 pmol/min/pmol P450. An activity adjustment factor (AAF) was calculated to account for differences between microsome batches and was used as a correction factor in the determination of the human in vivo hepatic clearance for MDZ, PH and AFB1. The hepatic blood clearance corrected for the AAF CLH,B,MDZ,AAF, CLH,B,PH,AAF CLH,B,AFB1,AAF(CYP3A4) and CLH,B,AFB1,AAF(CYP1A2) were determined in HLM at 44.1 L/h, 21.7 L/h, 40.0 L/h and 38.5 L/h. Finally, inhibition assays in HLM showed that 45% of the AFB1 metabolism was performed by CYP3A4/3A5 enzymes and 49% by CYP1A2 enzymes.".
- 01GPK9PZA2CDWAMX99KBCE81G1 author 0BAC47AC-F0EE-11E1-A9DE-61C894A0A6B4.
- 01GPK9PZA2CDWAMX99KBCE81G1 author 0D3B56D0-0947-11E4-AA83-18CA4B2F559A.
- 01GPK9PZA2CDWAMX99KBCE81G1 author 11556A76-F0EE-11E1-A9DE-61C894A0A6B4.
- 01GPK9PZA2CDWAMX99KBCE81G1 author 7340E12A-2AE5-11E3-A4E0-796A10BDE39D.
- 01GPK9PZA2CDWAMX99KBCE81G1 author F451D2E8-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GPK9PZA2CDWAMX99KBCE81G1 author F4CD454A-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GPK9PZA2CDWAMX99KBCE81G1 dateCreated "2023-01-12T15:31:26Z".
- 01GPK9PZA2CDWAMX99KBCE81G1 dateModified "2024-07-09T15:52:35Z".
- 01GPK9PZA2CDWAMX99KBCE81G1 name "Unravelling the pharmacokinetics of aflatoxin B1 : in vitro determination of Michaelis-Menten constants, intrinsic clearance and the metabolic contribution of CYP1A2 and CYP3A4 in pooled human liver microsomes".
- 01GPK9PZA2CDWAMX99KBCE81G1 pagination urn:uuid:c0762c2e-e835-4484-a134-abd5fe9f9850.
- 01GPK9PZA2CDWAMX99KBCE81G1 sameAs LU-01GPK9PZA2CDWAMX99KBCE81G1.
- 01GPK9PZA2CDWAMX99KBCE81G1 sourceOrganization urn:uuid:00b0e7cc-880c-4233-bf7f-37f0a7046536.
- 01GPK9PZA2CDWAMX99KBCE81G1 type A1.