Title

Biochemical Basis for the Extreme Sensitivity of Turkeys to Aflatoxin B1

Document Type

Article

Journal/Book Title/Conference

Toxicology and Applied Pharmacology

Volume

165

Issue

1

Publisher

Elsevier

Publication Date

2000

First Page

45

Last Page

62

DOI

10.1006/taap.2000.8926

Abstract

Poultry are the most susceptible food animal species to the toxic effects of the mycotoxin aflatoxin B1 (AFB1). Feed contaminated with even small amounts of AFB1 results in significant adverse health effects in poultry. The purpose of this study was to explain the biochemical mechanism(s) for this extreme sensitivity. We measured microsomal activation of AFB1 to the AFB1-8,9-epoxide (AFBO), the putative toxic intermediate, as well as cytosolic glutathione S-transferase (GST)-mediated detoxification of AFBO, in addition to other hepatic phase I and phase II enzyme activities, in 3-week-old male Oorlop strain turkeys. Liver microsomes prepared from these turkeys activated AFB1in vitro with an apparent Km of 109 μM and a Vmax of 1.25 nmol/mg/min. Preliminary evidence for the involvement of cytochromes P450 (CYP) 1A2 and, to a lesser extent, 3A4 for AFB1 activation was assessed by the use of specific mammalian CYP inhibitors. The possible presence of avian orthologues of these CYPs was supported by activity toward ethoxyresorufin and nifedipine, as well as by Western immunoblotting using antibodies to human CYPs. Cytosol prepared from turkey livers exhibited GST-mediated conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitrobenzene (DCNB), but at a much lower rate than that observed in other species. Western immunoblotting indicated the presence of α and ς class GSTs and another AFB1-detoxifying enzyme, AFB1-aldehyde reductase (AFAR). Turkey liver cytosol also had quinone oxidoreductase (QOR) activity. Importantly, cytosol exhibited no measurable GST-mediated detoxification of microsomally activated AFB1, indicating that turkeys are deficient in the most crucial AFB1-detoxification pathway. In total, our data indicate that the extreme sensitivity of turkeys to AFB1 may be attributed to a combination of efficient AFB1 activation and deficient detoxification by phase II enzymes, such as GSTs.

Comments

Originally published by Elsevier. Publisher's PDF available through remote link.