Date of Award

12-2021

Degree Type

Report

Degree Name

Master of Science (MS)

Department

Animal, Dairy, and Veterinary Sciences

Committee Chair(s)

Roger Coulombe (Committee Chair)

Committee

Roger Coulombe

Committee

Jeffery Hall

Committee

Kerry Rood

Abstract

Avian species are highly susceptible to the hepatotoxic mycotoxin aflatoxin B1 (AFB1). Domesticated turkeys are exquisitely sensitive, due to a combination of highly-efficient hepatic cytochrome P450 (CYP)-mediated bioactivation, and to dysfunctional alpha-class glutathione S-transferases (GSTAs) which typically detoxify the bioactivated electrophilic metabolite exo-AFB1-8,9-epoxide (AFBO). Wild turkeys are relatively resistant to AFB1 in large part due to expression of functional GSTAs. Quail, a related Galliforme, are slightly less sensitive in vivo to AFB1, but whether this is related to the hepatic metabolic profiles of these two critical enzymes has not been rigorously evaluated. The purpose of this study was to compare hepatic CYP-mediated bioactivation and GST-mediated detoxification activities toward AFB1 in Callipepla californica (HQ) and Coturnix japonica (JQ) against those from domesticated Broad-breasted White (BB) or Eastern Wild (EW) turkeys. Although Callipepla californica is commonly known as the California quail, the flock investigated in this study originated in Hawaii, hence use of the identifier “HQ” (noted above) that will be used throughout this report. Hepatic expression of CYP1A5 was significantly greater in both quail species, whereas there was no difference in CYP3A37 expression between species. Likewise, livers from both quail species expressed significantly greater GSTA3 than that from both turkey types, whereas turkeys expressed greater hepatic GSTA4 than those from both quail species. Kinetic analysis confirmed that liver microsomes from turkeys bioactivated AFB1 more efficiently (high Vmax, Kcat; low Km) than those from quail, whereas hepatic cytosols from quail were significantly more efficient in detoxifying AFBO than those from turkeys. Conversely, turkey hepatic cytosols were more efficient than quail at detoxifying GST indicator substrates 1-chloro-2,4-dinitrobenzene (CDNB), ethacrynic acid (ECA), and cumene hydroperoxide (CHP), but not 1,2-dichloro-4-nitrobenzene (DCNB), indicating greater presence of GST isoforms not relevant to AFB1 detoxification. In total, our data shows that the relative resistance of quail compared to turkeys is reflected in the relatively lower in vitro bioactivation and higher detoxification activities.

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