PMID- 31586656
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200217
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Linking)
VI  - 135
DP  - 2020 Jan
TI  - In vitro metabolism of pyrrolizidine alkaloids - Metabolic degradation and GSH 
      conjugate formation of different structure types.
PG  - 110868
LID - S0278-6915(19)30658-1 [pii]
LID - 10.1016/j.fct.2019.110868 [doi]
AB  - Pyrrolizidine alkaloid (PA) forming plants are found worldwide and may 
      contaminate food products at levels being of concern for human health. Due to the 
      high biodiversity of PA producing plants many different types of PA structures 
      are formed. PAs themselves are not toxic but require metabolic activation to 
      exert toxicity. To investigate if the structure of the PAs affects their in vitro 
      metabolism, we incubated a set of 22 PAs and compared the degradation rates and 
      the amount of formed glutathione (GSH) conjugates. With human liver microsomes, 
      no metabolic degradation of monoesters was found. Degradation rates of diester 
      PAs tended to correlate with their hydrophilicity, whereby the more polar and 
      branched-chained PAs exhibited lower degradation. There was a trend towards 
      higher degradation rates in the presence of rat liver microsomes, but the GSH 
      conjugate levels were similar. Although an effective degradation seems to be 
      related with high GSH conjugate levels, no clear correlation between both 
      parameters could be deduced. For both species no GSH conjugates, or only trace 
      amounts, were formed from monoesters. However, for both open-chained as well as 
      cyclic diesters GSH conjugates were detected and determined levels were 
      comparable for both ester types without major structure-dependent differences.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Geburek, Ina
AU  - Geburek I
AD  - German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, 
      Berlin, Germany; University of Kaiserslautern, Food Chemistry and Toxicology, 
      Erwin-Schrodinger-Strasse 52, 67663, Kaiserslautern, Germany.
FAU - Preiss-Weigert, Angelika
AU  - Preiss-Weigert A
AD  - German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, 
      Berlin, Germany.
FAU - Lahrssen-Wiederholt, Monika
AU  - Lahrssen-Wiederholt M
AD  - German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, 
      Berlin, Germany.
FAU - Schrenk, Dieter
AU  - Schrenk D
AD  - University of Kaiserslautern, Food Chemistry and Toxicology, 
      Erwin-Schrodinger-Strasse 52, 67663, Kaiserslautern, Germany.
FAU - These, Anja
AU  - These A
AD  - German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589, 
      Berlin, Germany. Electronic address: anja.these@bfr.bund.de.
LA  - eng
PT  - Journal Article
DEP - 20191003
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Pyrrolizidine Alkaloids)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Glutathione/*metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Microsomes, Liver/metabolism
MH  - Molecular Structure
MH  - Pyrrolizidine Alkaloids/chemistry/*metabolism
MH  - Rats
EDAT- 2019/10/07 06:00
MHDA- 2020/02/18 06:00
CRDT- 2019/10/07 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/09/30 00:00 [revised]
PHST- 2019/10/02 00:00 [accepted]
PHST- 2019/10/07 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2019/10/07 06:00 [entrez]
AID - S0278-6915(19)30658-1 [pii]
AID - 10.1016/j.fct.2019.110868 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2020 Jan;135:110868. doi: 10.1016/j.fct.2019.110868. Epub 2019 
      Oct 3.