The fates of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice.
In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, 3H-FX or 3H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given 3H-FX, but mainly via the feces in mice given 3H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of 3H-FX or 3H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in 3H-FX-administered than 3H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with 3H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.
Poapolathep
Amnart
A
Department of Veterinary Pathology, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Sugita-Konishi
Yoshiko
Y
Doi
Kunio
K
Kumagai
Susumu
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009183:Mycotoxins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution; D014255:Trichothecenes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D014316:Tritium / Q000493:pharmacokinetics
D009183:Mycotoxins; D014255:Trichothecenes; D014316:Tritium; C002469:fusarenon-X; C038405:nivalenol