Metabolism of T-2 toxin in vascularly autoperfused jejunal loops of rats.
The intestinal metabolism of T-2 toxin, a major trichothecene mycotoxin, was investigated in rats using the method of the vascularly autoperfused jejunal loop in situ. Tritium-labeled T-2 toxin was injected into the tied-off intestinal segments at a dose of 5 or 500 nmol, respectively. T-2 toxin and its metabolites in the blood draining from the jejunal loops, in the intestinal lumen, and in the intestinal tissue were determined by HPLC and GLC-MS. There was an extensive metabolic degradation of T-2 toxin, the metabolite pattern being similar for the two dosage levels. During the experimental period of 50 min only some 2% of the total dose appeared in the effluent plasma as unchanged T-2 toxin. Likewise at the end of the experiments unchanged T-2 toxin in the intestinal lumen and tissue was present in minute amounts only (less than 1% of the dose). HT-2 toxin was the main metabolite. About 25% of the total radioactivity administered appeared in the effluent plasma as HT-2 toxin, 18% in the lumen and 10% in the tissue. 3'-OH-HT-2 toxin accounted for 4-7% (effluent plasma), 5% (lumen), and 2% (tissue) of the total dose. Furthermore small amounts (less than 2% of the dose) of 3'-OH-T-2 toxin, T-2 tetraol, and 4-deacetylneosolaniol were found. No glucuronide or sulfate conjugates could be detected. In the jejunal segments which had been exposed to the 5-nmol dose only minimal morphological alterations were observed. On the other hand, in jejunal segments exposed to the high dose marked tissue damage was present. Nevertheless the gut tissue retained its ability to metabolize T-2 toxin. From the present results it is concluded that T-2 toxin is subject to a marked presystemic first pass effect after oral ingestion in vivo.
Conrady-Lorck
S
S
Walther-Straub-Institute for Pharmacology and Toxicology, University of Munich, Federal Republic of Germany.
Gareis
M
M
Feng
X C
XC
Amselgruber
W
W
Forth
W
W
Fichtl
B
B
D000818:Animals; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D013605:T-2 Toxin / Q000378:metabolism* / Q000633:toxicity
D005965:Glucuronates; D012717:Sesquiterpenes; D013605:T-2 Toxin