title: Species differences in the hepatic biotransformation of zearalenone.
abstract: Zearalenone (ZEA), a Fusarium toxin, is frequently found in animal feed materials. It is known to exert oestrogenic effects in all animals tested but susceptibility varies between species, possibly reflecting differences in the metabolic processing of ZEA, which predominantly involves hydroxylations, assumed to be catalysed by 3alpha- and 3beta- hydroxysteroid dehydrogenases, as well as conjugation with glucuronic acid. In this study, the biotransformation of ZEA by hepatic subcellular fractions of various domestic animals was investigated and compared to the rat. Notable inter-species differences in terms of the rate of absolute and relative metabolite production in the different subcellular fractions were identified. The highest amount of alpha-zearalenol (alpha-ZOL) was produced by pig hepatic microsomes (V(max)=795.8+/-122.7pmol/mg/min), whereas in chicken microsomes the highest amounts of beta-zearalenol (beta-ZOL) (V(max)=1524+/-29.7pmol/mg/min) could be measured. Except for sheep and cattle, the efficiency of alpha-ZOL production (expressed as the ratio of apparent V(max)/k(m)) was higher in the microsomal fraction compared to the post-mitochondrial fraction. In contrast, the apparent efficiency of beta-ZOL production was high in pigs, cattle, chickens and rats, but very low in sheep. Conjugation of ZEA with glucuronic acid was investigated, and the results indicated significant inter-species differences in the rate of glucuronidation, which was saturable at low concentrations in all species tested, except pigs. The significant differences between the percentages of glucuronidation of ZEA, alpha-ZOL, and beta-ZOL suggest not only differences in the affinity of the individual substrate, but might also indicate the presence of different isoforms of uridine diphosphate glucuronyl transferases (UDPGTs). The results are of clinical relevance, as they contribute to the understanding of the species-specific susceptibility towards exposure to ZEA.
authors.affiliation: Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands. hassanmalekinejad@yahoo.com
authors.forename: H
authors.initials: H
authors.lastname: Malekinejad
authors.forename: R
authors.initials: R
authors.lastname: Maas-Bakker
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D000821:Animal Feed; D000818:Animals; D001711:Biotransformation; D002417:Cattle; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000378:metabolism*; D005506:Food Contamination; D008099:Liver / Q000378:metabolism*; D051381:Rats; D012756:Sheep; D013045:Species Specificity; D013552:Swine; D015025:Zearalenone / Q000378:metabolism*
chemical_list: D004968:Estrogens, Non-Steroidal; D015025:Zearalenone