title: Inhibition of aflatoxin M1 production by bovine hepatocytes after intervention with oltipraz.
abstract: It is well known that cattle ingesting aflatoxin B1 contaminated feed commodities excrete aflatoxin M1 into their milk. As aflatoxin M1 originates from hepatic metabolism, measures to prevent aflatoxin M1 formation need to be directed to either the immobilization of aflatoxin B1 in the gastrointestinal tract or the modification of hepatic metabolism of aflatoxin B1. Here we studied the influence of oltipraz and a second dithiolthione, (1,2) dithiolo (4,3-c)-1,2-dithiole-3,6 dithione (DDD) on bovine hepatic aflatoxin B1 biotransformation. Oltipraz inhibited aflatoxin B1 metabolism as no aflatoxin M1 and no aflatoxin B1-dihydrodiol, the second metabolite found in bovine hepatocytes, was formed. DDD did not significantly inhibit aflatoxin B1 metabolism. It could be demonstrated that the inhibition of aflatoxin B1 metabolism was due to the inhibition of several cytochrome P450 enzyme activities by oltipraz. In contrast, DDD inhibited only ethoxyresorufin O-deethylation activity. These findings suggest a high efficacy of oltipraz in inhibiting aflatoxin M1 contamination of milk from dairy cows exposed to aflatoxin B1 contaminated feeds.
authors.affiliation: National Institute of Public Health and the Environment Center for Substances and Risk Assessment, The Netherlands. Mariella.Kuilman@rivm.nl
authors.forename: M E
authors.initials: ME
authors.lastname: Kuilman
authors.forename: R F
authors.initials: RF
authors.lastname: Maas
authors.forename: F M
authors.initials: FM
authors.lastname: Woutersen-van Nijnanten
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D016607:Aflatoxin M1 / Q000096:biosynthesis*; D000821:Animal Feed; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002417:Cattle; D018929:Cell Culture Techniques; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005506:Food Contamination; D008099:Liver / Q000166:cytology* / Q000187:drug effects; D008892:Milk / Q000737:chemistry*; D011719:Pyrazines / Q000494:pharmacology*; D013871:Thiones; D013876:Thiophenes
chemical_list: D016588:Anticarcinogenic Agents; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D016607:Aflatoxin M1; C026209:oltipraz; D003577:Cytochrome P-450 Enzyme System