Lack of hepatic microsomal metabolism of deoxynivalenol and its metabolite, DOM-1.
Rat hepatic microsomal preparations were used to study the metabolism of deoxynivalenol (DON) and its metabolite 3 alpha,7 alpha,15-trihydroxytrichothec-9,12-dien-8-one (DOM-1). The N-demethylation of ethylmorphine was monitored to assess the viability of the mixed-function oxidase. DON was incubated with microsomes and an NADPH-generating system. Samples were removed from the incubation system and analysed for DON using an HPLC equipped with a UV detector. After incubation for 30 min, there was no evidence of disappearance of DON or of the presence of new metabolites; neither was microsomal NADPH oxidation altered by the addition of DON. Rat and pig hepatic microsomal preparations were used to assess DON glucuronidation, using p-nitrophenol disappearance to check the viability of the microsomal glucuronidating system. When DON was incubated with microsomes and 14C-labelled uridine 5'-diphosphoglucuronic acid, no radioactivity was detected in the TLC zone where the glucuronide was expected. Three rats and one pig were dosed orally with 2 mg DON/kg and samples of their urine and faeces were extracted and incubated with beta-glucuronidase or with buffer only. No differences in DON or DOM-1 concentrations were detected between samples incubated with or without beta-glucuronidase. These results suggest that DON was neither bioactivated to a more toxic product nor oxidized to a less toxic compound by the rat hepatic mixed-function oxidase system. Likewise, DOM-1 was not reactivated or metabolized by this system. Neither DON nor DOM-1 glucuronides were formed either in in vitro liver systems or in vivo.
D000818:Animals; D005243:Feces / Q000378:metabolism; D005965:Glucuronates / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D013552:Swine; D014255:Trichothecenes / Q000378:metabolism*
D005965:Glucuronates; D012717:Sesquiterpenes; D014255:Trichothecenes; C048238:deepoxy-deoxynivalenol; D006899:Mixed Function Oxygenases; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C007262:deoxynivalenol