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.

Key words:

• aflatoxin B₁
• aflatoxin M₁
• oltipraz
• bovine metabolism
• hepatocytes

Notes

Corresponding author: J. Fink‐Gremmels, Department of Veterinary Pharmacology, Pharmacy and Toxicology, Utrecht University, P.O. Box 80152, 3508 TD Utrecht, the Netherlands. Telephone: [phone], fax [phone], email [email protected]

Current address: National Institute of Public Health and the Environment, Center for Substances and Risk Assessment, P.O. Box 1, 3720 BA Bilthoven, the Netherlands. Telephone: [phone], fax: [phone], email: [email protected]