Trapping of short-lived electrophilic metabolites of pyrrolizidine alkaloids escaping from perfused rat liver.
It has been shown that a short-lived pyrrolic metabolite in fluid flowing out of isolated rat liver perfused with the pyrrolizidine alkaloid, monocrotaline, could be trapped by covalent reaction with a bed of immobilized thiol (thiol-sepharose). Larger amounts of other pyrrolic metabolites, also in the fluid, were not trapped. This provided the first direct support for the widely held hypothesis that reactive pyrrolizidine alkaloid metabolites (dehydro-alkaloids) escape from the liver to damage the lungs of rats in vivo. The relatively smaller proportion of pyrrolic metabolite from retrorsine which could be trapped in this way was consistent with the known lack of pneumotoxicity of this alkaloid. The procedure described should be suitable for trapping other types of electrophilic metabolites.
Mattocks
A R
AR
Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.
Legg
R F
RF
Jukes
R
R
D000818:Animals; D002855:Chromatography, Thin Layer; D004347:Drug Interactions; D008099:Liver / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline / Q000031:analogs & derivatives*; D010634:Phenobarbital / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011763:Pyrrolizidine Alkaloids; C014114:monocrotaline pyrrole; D016686:Monocrotaline; C003300:retrorsine; D010634:Phenobarbital