Chemoprotective role of molybdo-flavoenzymes against xenobiotic compounds

Abstract EN

Aldehyde oxidase (AO) and xanthine oxidoreductase (XOR) are molybdo-flavoenzymes (MFEs) involved in the oxidation of hundreds of many xenobiotic compounds of which are drugs and environmental pollutants.

Mutations in the XOR and molybdenum cofactor sulfurase (MCS) genes result in a deficiency of XOR or dual AO/XOR deficiency respectively.

At present despite AO and XOR being classed as detoxification enzymes the definitive experimental proof of this has not been assessed in any animal thus far.

The aim of this project was to evaluate ry and ma-l strains of Drosophila melanogaster as experimental models for XOR and dual AO/XOR deficiencies respectively and to determine if MFEs have a role in the protection against chemicals.

In order to test the role of the enzymes in chemoprotection, MFE substrates were administered to Drosophila in media and survivorship was monitored.

It was demonstrated that several methylated xanthines were toxic to XOR-deficient strains.

In addition a range of AO substrates including N-heterocyclic pollutants and drugs were significantly more toxic to ma-l AO-null strains.

This study therefore provides definitive proof that both AO and XOR are involved in detoxification.

-