Fate of TR-2, the hepatic metabolite of the tremorgenic mycotoxin verruculogen, in sheep.
1. Verruculogen is eliminated in bile after transformation to TR-2, only a trace of which was excreted as such in faeces of sheep given verruculogen per os. Negligible TR-2 was present free in urine; no glucuronide was found. 2. An isomer of TR-2, a minor component of the bile of sheep given verruculogen, has been defined by 1H-n.m.r. spectroscopy and the isomerism involves the disposition of the two adjacent hydroxyl groups with a concomitant change in the conformation of the ring adjacent to the indole. 3. 14C-TR-2, added to the perfusate of isolated rat liver, was excreted unchanged in the bile, implying no significant loss of any biliary TR-2 subject to enterohepatic recycling in vivo. 4. 14C-TR-2 incubated anaerobically in sheep ileum contents was 95% transformed into more polar metabolites, the majority of the radiolabelled metabolites isolated being water soluble. 5. The principal fate of biliary TR-2 is as a metabolic substrate for the intestinal microflora.
Laws
I
I
Biochemistry Department, Imperial College, University of London, UK.
Mantle
P G
PG
Rodrigues
L
L
Penny
R H
RH
D000818:Animals; D001646:Bile / Q000378:metabolism; D005243:Feces / Q000032:analysis; D005260:Female; D007082:Ileum / Q000378:metabolism; D007211:Indoles / Q000493:pharmacokinetics* / Q000652:urine; D007536:Isomerism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009183:Mycotoxins / Q000493:pharmacokinetics* / Q000652:urine; D010477:Perfusion; D012756:Sheep
D007211:Indoles; D009183:Mycotoxins; C009658:verruculogen; C039287:TR-2 mycotoxin