Biochemical Basis for the Extreme Sensitivity of Turkeys to Aflatoxin B1

The role of selected cytochrome P450 enzymes on the bioactivation of aflatoxin B1 by duck liver microsomes

“…A possible explanation for this apparent inconsistency may be that the duck CYP3A4 orthologue does not exhibit the same sensitivity to specific inhibitors as the human orthologue. Klein et al (2000) showed inhibition of AFBO formation in turkey liver microsomes using 17a-ethynylestradiol. It is possible that the CYP3A4 duck orthologue might be sensitive to 17a-ethynylestradiol, as is the turkey orthologue, but more studies are needed to verify this hypothesis.…”

Biotransformation of Aflatoxin B1 and Its Relationship with the Differential Toxicological Response to Aflatoxin in Commercial Poultry Species

“…The role of CYP1A5 turkey activity on the bioactivation of AFB1 in turkeys is further supported by the work of Guarisco et al (2008) who found that dietary supplementation of the antioxidant butylated hydroxytoluene (BHT) partially protected against the adverse effects of AFB1, an effect that was accompanied by a reduction in EROD and MROD activities in the liver. In regards to CYP3A4, Klein et al (2000) found that this enzyme plays a minor role in the bioactivation of AFB1 in turkeys. This finding, however, could not be substantiated by Diaz et al (2010a) who found no correlation between nifedipine oxidation (an indicator of CYP3A4 activity) and AFBO formation, and no effect on AFBO formation when the prototype inhibitor of human CYP3A4 activity troleandomycin was used.…”

“…Even though the studies of Klein et al (2000) in turkeys, and Lozano & Diaz (2006) in turkeys, chickens, ducks and quail had clearly demonstrated that hepatic microsomes from poultry were capable of bioactivating AFB1 into AFBO, there was only scarce information on the specific CYP450 enzymes responsible for this biotransformation reaction and it was limited to turkeys (Klein et al, 2000;Yip & Coulombe, 2006). In contrast, in humans, at least three CYP450s had been identified as responsible for AFB1 bioactivation to AFBO (CYP1A2, CYP2A6 and CYP3A4) (Omiecinski et al, 1999;Hasler et al, 1999), and there was evidence that the CYP3A4 human enzyme was the most efficient .…”

“…The f a c t t h a t f o u r C Y P 4 5 0 e n z y m e s a r e i n v o l v e d i n A F B 1 b i o a c t i v a t i o n i n d u c k s c o u l d partially explain the high sensitivity of this species to AFB1. In turkey liver, AFB1 was reported to be activated to AFBO by a CYP 1A ortholog (Klein et al, 2000) that later was identified as the turkey CYP1A5 on the basis of its 94.7% sequence identity to the CYP1A5 from chicken liver (Yip & Coulombe, 2006). This enzyme was suggested to correspond to the human ortholog CYP1A2 (Yip & Coulombe, 2006).…”

Bird Glutathione S-transferases: Endogenous and Exogenous Toxic Insults Read more at http://nexusacademicpublishers.com/table_contents_detail/4/872/html#CUM6EltbRFTzsEeL.99

“…Domestic turkeys (Meleagris gallopavo) are one of the most susceptible species known to AFB1 (Klein et al, 2000;Rawal et al, 2010). The efficiency of GST conjugation is a principal ''rate-limiting'' determinant for AFB1 action in individuals and species (Ilic et al, 2010).…”