Patulin reduces glutathione level and enzyme activities in rat liver slices.
In the present study, an attempt was made to identify glutathione (GSH) adducts of patulin in precision-cut rat liver slices, which were used as a model system to study the metabolism and biological effects of this mycotoxin. Patulin disappeared in the slices but none of the GSH adducts, previously demonstrated in the chemical reaction of patulin with GSH, could be detected by HPLC. After incubation with various concentrations of patulin, a concentration-dependent decline of the GSH level was observed in the slices. For example, only 25% of the GSH of controls was found with 200 microM patulin. The activities of glutathione-S-transferase (GST) and of drug metabolizing phase I and phase II enzymes, assayed by the hydroxylation and conjugation of testosterone, were also reduced. On the other hand, incubation with patulin markedly increased lipid peroxidation in the slices. The effects of patulin on enzyme activities and lipid peroxidation may be a consequence of the GSH decline, which cannot be accounted for by a direct reaction of patulin with GSH due to the high concentration of GSH in hepatocytes. The decrease of GSH level and GST activity may be related to the putative mutagenic and carcinogenic potential of patulin.
Pfeiffer
Erika
E
Institute of Food Chemistry and Toxicology, Department of Chemistry and Biosciences, University of Karlsruhe, Karlsruhe, Germany.
Diwald
Tabea T
TT
Metzler
Manfred
M
D000818:Animals; D005978:Glutathione / Q000032:analysis* / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism*; D006900:Hydroxylation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009183:Mycotoxins / Q000494:pharmacology*; D010365:Patulin / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism
D009183:Mycotoxins; D013739:Testosterone; D010365:Patulin; D007770:L-Lactate Dehydrogenase; D005982:Glutathione Transferase; D005978:Glutathione