title: Biochemical factors underlying the age-related sensitivity of turkeys to aflatoxin B(1).
abstract: Poultry are some of the most sensitive species to the toxic effects of aflatoxin B(1) (AFB(1)), and younger poultry are more sensitive to this mycotoxin. To elucidate the mechanisms for this age-related susceptibility, various enzyme activities relevant to AFB(1) were measured in liver microsomes prepared from male turkeys 9, 41 and 65 days of age. Hepatic microsomal o-dealkylation of methoxy- and pentoxyresorufin significantly increased, while that of ethoxyresorufin decreased with age. Microsomal AFB(1) activation to the reactive AFB(1)-8,9-epoxide (AFBO) was most efficient in the youngest birds, with apparent K(m) and V(max) values of 168 and 19, 110 and 6, and 116 microM and 10 nmol/mg/min for 9, 41 and 65-day-old birds, respectively. The activity of hepatic cytosolic glutathione S-transferases (GSTs) was deficient in the youngest age group, but were higher in the older groups. There was also an age-related increase in the expression of GST isoforms Yc, Yc(2), as well as AFB(1)-aldehyde reductase (AFAR). However, livers from all ages lacked specific GST-mediated conjugation of AFBO, indicating that turkeys are deficient in this key AFB(1)-detoxification pathway. Our data indicate that efficient activation may underlie the extreme sensitivity of young turkeys to the toxic effects of AFB(1).
authors.affiliation: Department of Veterinary Sciences, and Graduate Program in Toxicology, Utah State University, Logan, UT 84322-4620, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Klein
authors.forename: Terry R
authors.initials: TR
authors.lastname: Van Vleet
authors.forename: Jeffery O
authors.initials: JO
authors.lastname: Hall
authors.forename: Roger A
authors.initials: RA
authors.lastname: Coulombe
mesh_terms: D016604:Aflatoxin B1 / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000633:toxicity*; D000367:Age Factors; D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001711:Biotransformation; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003600:Cytosol / Q000201:enzymology; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014422:Turkeys / Q000378:metabolism*
chemical_list: D004852:Epoxy Compounds; D007527:Isoenzymes; D016604:Aflatoxin B1; C082765:aflatoxin B1 aldehyde reductase; D000449:Aldehyde Reductase; D001189:Aryl Hydrocarbon Hydroxylases; D005982:Glutathione Transferase