In vitro and in vivo hepatic metabolism of the fungal neurotoxin penitrem A.
Penitrem A is a potent neurotoxin produced by several species in the genus Penicillium, which primarily affects the central nervous system. The toxin has several effects on neurotransmitter release, both at the central and peripheral level, as well as on ion channels. We have evaluated the hepatic metabolism of penitrem A by rat hepatocytes and rat-liver microsomes in vitro. In addition, we have conducted an in vivo study in mice and determined metabolites in several organs. According to our results, penitrem A is extensively metabolized in the liver to at least five metabolites more hydrophilic than the parent compound.
Moldes-Anaya
Angel
A
Section of Chemistry and Toxicology, National Veterinary Institute, Oslo, Norway. angel.moldes-anaya@vetinst.no
Wilkins
Alistair L
AL
Rundberget
Thomas
T
Faeste
Christiane K
CK
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D009183:Mycotoxins / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D010407:Penicillium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009183:Mycotoxins; D009498:Neurotoxins; C003626:tremortin