Effects of dietary butylated hydroxytoluene on aflatoxin B1-relevant metabolic enzymes in turkeys.
We have shown previously that the extreme sensitivity of turkeys to aflatoxin B(1) (AFB(1)) is due to a combination of efficient AFB(1) activation by cytochrome P450s (CYPs) 1A and deficient detoxification by glutathione S-transferases (GSTs). Phenolic antioxidants such as butylated hydroxytoluene (BHT) have been shown to be chemoprotective in some animal models due, in part, to modulation of AFB(1)-relevant phase I and/or phase II activities, and we wished to determine whether BHT has a similar effect in turkeys. Ten-day-old male turkeys were maintained on diets amended with 1000 or 4000 ppm of BHT for 10 days, then sampled. Hepatic microsomal CYP 1A activity as well as conversion of AFB(1) to the putative toxic metabolite, the exo-AFB(1)-8,9-epoxide (AFBO), were significantly lower compared with control. Conversely, dietary BHT significantly increased activities of several isoforms of hepatic cytosolic GST, as well quinone oxidoreductase (QOR). Western immunoblotting confirmed that dietary BHT increased expression of homologues to rodent GST isoforms Yc1, Yc2 and Ya. There was, however, no observable BHT-related increase in GST-mediated specific conjugation with microsomally-generated AFBO. In total, our data indicates that dietary BHT modulates a variety of AFB(1)-relevant phase I and phase II enzymes, while having no measurable effect towards specific AFB(1) detoxification by GST.
Klein
P J
PJ
Department of Veterinary Sciences, and Graduate Program in Toxicology, Utah State University, Logan 84322-4620, USA.
Van Vleet
T R
TR
Hall
J O
JO
Coulombe
R A
RA
D016604:Aflatoxin B1 / Q000009:adverse effects*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002084:Butylated Hydroxytoluene / Q000008:administration & dosage / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000494:pharmacology; D005982:Glutathione Transferase / Q000494:pharmacology*; D007527:Isoenzymes; D008297:Male; D014422:Turkeys / Q000502:physiology*
D000975:Antioxidants; D007527:Isoenzymes; D002084:Butylated Hydroxytoluene; D016604:Aflatoxin B1; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase