T-2 toxin is hydroxylated by chicken CYP3A37

Area of Science:

• Veterinary toxicology
• Drug metabolism
• Mycotoxicology

Background:

• T-2 toxin is a harmful mycotoxin found in crops and animal feed.
• Understanding T-2 toxin metabolism in food animals is crucial for human health.
• Chicken CYP3A37 is a cytochrome P450 enzyme with potential metabolic roles.

Purpose of the Study:

• To investigate the metabolic capacity of chicken CYP3A37 in T-2 toxin metabolism.
• To determine the kinetic parameters of T-2 toxin hydroxylation by chicken CYP3A37.
• To assess the inhibitory effects of ketoconazole on this metabolic pathway.

Main Methods:

• Utilized reconstituted bacterial enzymes for in vitro metabolism studies.
• Measured the conversion of T-2 toxin to 3 -OH T-2.
• Assessed the inhibitory effect of ketoconazole on T-2 hydroxylation.
• Examined the N-demethylation of erythromycin as a CYP3A-specific activity.

Main Results:

• Chicken CYP3A37 demonstrated the ability to convert T-2 toxin to 3 -OH T-2.
• The apparent Km for T-2 hydroxylation by CYP3A37 was determined to be 15.29 μM.
• Ketoconazole strongly inhibited T-2 hydroxylation activity with an IC50 of 0.11 μM.
• CYP3A37 also catalyzed erythromycin N-demethylation, indicating a broad substrate spectrum.

Conclusions:

• Chicken CYP3A37 plays a role in T-2 toxin metabolism.
• The enzyme exhibits kinetic properties and inhibition patterns similar to other CYP3A enzymes.
• Chicken CYP3A37 may possess a broad substrate spectrum, analogous to human CYP3A4.
• These findings contribute to understanding T-2 toxin's fate in food animals and potential human health implications.