Biochemical basis for the extreme sensitivity of turkeys to aflatoxin B-1

Poultry are the most susceptible food animal species to the toxic effects o f the mycotoxin aflatoxin B-1 (AFB(1)). Feed contaminated with even small a mounts of AFB(1) results in significant adverse health effects in poultry. The purpose of this study was to explain the biochemical mechanism(s) for t his extreme sensitivity. We measured microsomal activation of AFB(1) to the AFB(1)-8,9-epoxide (AFBO), the putative toxic intermediate, as well as cyt osolic 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 turke ys activated AFB(1) in vitro with an apparent K-m of 109 mu M and a V-max o f 1.25 nmol/mg/min. Preliminary evidence for the involvement of cytochromes P450 (CYP) 1A2 and, to a lesser extent, 3A4 for AFB(1) activation was asse ssed by the use of specific mammalian CYP inhibitors. The possible presence of avian orthologues of these CYPs was supported by activity toward ethoxy resorufin and nifedipine, as well as by Western immunoblotting using antibo dies to human CYPs. Cytosol prepared from turkey livers exhibited GST-media ted conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and 3,4-dichloronitro benzene (DCNB), but at a much lower rate than that observed in other specie s. Western immunoblotting indicated the presence of alpha and sigma class G STs and another AFB(1)-detoxifying enzyme, AFB(1)-aldehyde reductase (AFAR) . Turkey liver cytosol also had quinone oxidoreductase (QOR) activity. Impo rtantly, cytosol exhibited no measurable GST-mediated detoxification of mic rosomally activated AFB(1), indicating that turkeys are deficient in the mo st crucial AFB(1)-detoxification pathway. In total, our data indicate that the extreme sensitivity of turkeys to AFB(1) may be attributed to a combina tion of efficient AFB(1) activation and deficient detoxification by phase I I enzymes, such as GSTs. (C) 2000 Academic Press.