Tissue distribution and excretion of myosmine after i.v. administration to Long-Evans rats using quantitative whole-body autoradiography.
Occurrence of the tobacco alkaloid myosmine has been proven in various staple foods, vegetables and fruits. Myosmine can be easily activated by nitrosation yielding 4-hydroxy-1-(3-pyridyl)-butanone (HPB) and the esophageal carcinogen N'-nitrosonornicotine. Most of the reaction products after myosmine peroxidation were also identified as urinary metabolites after oral administration to rats. Whole-body autoradiography with freeze dried or multiple solvent extracted tissue sections was used to trace [2'-(14)C]myosmine (0.1 mCi/kg bw) 0.1, 0.25, 1, 4 and 24 h after i.v. injection in Long-Evans rats. In addition, in vitro binding of radioactivity to esophageal and eye tissue was determined and excretion of radioactivity via urine and feces was quantified. Radioactivity is rapidly eliminated by renal excretion. Approximately 30% of the administered radioactivity was recovered in urine within the first 4 h and excretion with urine (72%) and feces (15%) was nearly complete after 24 h. A rapid concentration of radioactivity can be seen in the stomach and in the salivary and lachrymal glands. Rats killed 1 and 4 h after treatment showed by far the highest labeling in the accessory genital gland. High levels of nonextractable radioactivity were present in esophageal tissue and melanin. The half lives for the disappearance of radioactivity from various tissues are in the order of about 1 h. Eye and esophagus sections both showed nonextractable labeling after in vitro incubation with (14)C-myosmine. In conclusion, the toxicological significance of myosmine accumulation in esophagus and accessory genital gland requires further investigations. Hair analysis might be applicable for myosmine biomonitoring, because of possible enrichment in melanin containing tissues.
Glas
Susanna
S
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Goethestrasse 33, 80336, Munich, Germany. stty@freenet.de
Tyroller
Stefan
S
Zwickenpflug
Wolfgang
W
Steiner
Kurt
K
Kiefer
Gudrun
G
Richter
Elmar
E
D000470:Alkaloids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D004947:Esophagus / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D008543:Melanins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D014018:Tissue Distribution
D000470:Alkaloids; D008543:Melanins; C002398:myosmine