Inhibition of aflatoxin M-1 production by bovine hepatocytes after intervention with oltipraz

It is well known that cattle ingesting aflatoxin B-1 contaminated feed comm odities excrete aflatoxin M-1 into their milk. As aflatoxin M-1 originates from hepatic metabolism, measures to prevent aflatoxin M-1 formation need t o be directed to either the immobilization of aflatoxin B-1 in the gastroin testinal tract or the modification of hepatic metabolism of aflatoxin B1. H ere 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 aflatoxi n B-1 biotransformation. Oltipraz inhibited aflatoxin B-1 metabolism as no aflatoxin M-1 and no aflatoxin B-1-dihydrodiol, the second metabolite found in bovine hepatocytes,was formed. DDD did not significantly inhibit aflato xin B-1 metabolism. It could be demonstrated that the inhibition of aflatox in B-1 metabolism was due to the inhibition of several cytochrome P450 enzy me activities by oltipraz. In contrast, DDD inhibited only ethoxyresorufin, O-deethylation activity. These findings suggest a high efficacy of oltipra z in inhibiting aflatoxin M-1 contamination of milk from dairy cows exposed to aflatoxin B-1 contaminated feeds.