Document Detail


Lack of hepatic microsomal metabolism of deoxynivalenol and its metabolite, DOM-1.
MedLine Citation:
PMID:  3583156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
L M Côté; W Buck; E Jeffery
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  25     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  1987 Apr 
Date Detail:
Created Date:  1987-07-09     Completed Date:  1987-07-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  291-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Feces / metabolism
Glucuronates / biosynthesis
Male
Microsomes, Liver / enzymology,  metabolism*
Mixed Function Oxygenases / metabolism
NADH, NADPH Oxidoreductases / metabolism
NADPH Oxidase
Rats
Rats, Inbred Strains
Sesquiterpenes / metabolism*
Swine
Trichothecenes / metabolism*
Grant Support
ID/Acronym/Agency:
RR05460/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Glucuronates; 0/Sesquiterpenes; 0/Trichothecenes; 51481-10-8/deoxynivalenol; 88054-24-4/deepoxy-deoxynivalenol; EC 1.-/Mixed Function Oxygenases; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.3.1/NADPH Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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