In vivo metabolism of retrorsine and retrorsine-N-oxide.
The in vivo metabolism and excretion of the urinary metabolites from the pyrrolizidine alkaloids (PAs), retrorsine (RET) and retrorsine-N-oxide (RET-NO) have been studied in rats. Isatinecic acid (INA), pyrrolic metabolites, N-oxides and retronecine accounted for 31.0, 10.3, 10.8 and 0.39% of the administered RET. Predosing rats with triorthocresyl phosphate (TOCP), had no effect on the excretion of pyrrolic metabolites and INA. Phenobarbital (PB) increased the excretion of both pyrrolic metabolites and INA with a corresponding decrease in the excretion of RET and N-oxides; the retronecine levels remained unaltered. When RET-NO was administered i.p., the urinary levels of pyrrolic metabolites, INA and RET were decreased relative to those treated with RET. The p.o. administration of RET-NO produced significantly higher levels of pyrrolic metabolites, INA and RET. These results suggest that esterase hydrolysis plays a minor role in the formation of INA and that a common metabolic pathway may exist between pyrrolic metabolites and INA formation.
Chu
P S
PS
Department of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.
Lamé
M W
MW
Segall
H J
HJ
D000818:Animals; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003998:Dicarboxylic Acids / Q000378:metabolism; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D010947:Plants, Toxic; D011758:Pyrroles / Q000737:chemistry / Q000652:urine; D011763:Pyrrolizidine Alkaloids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012674:Senecio / Q000737:chemistry; D014317:Tritolyl Phosphates / Q000494:pharmacology
D003998:Dicarboxylic Acids; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; D014317:Tritolyl Phosphates; C074569:isatinecic acid; C013577:isatidine; C025541:tri-o-cresyl phosphate; C003300:retrorsine; D010634:Phenobarbital