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Tissue distribution and excretion of myosmine after i.v. administration to Long–Evans rats using quantitative whole-body autoradiography

  • Toxicokinetics and Metabolism
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Abstract

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′-14C]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 14C-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.

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Acknowledgments

We thank Merck KGaA, Institute of Drug Metabolism and Pharmakokinetics (Grafing, Germany) for providing their knowledge and equipment for the autoradiography studies. This work was supported in part by the Deutsche Forschungsgemeinschaft (Project No. ZW 59/2–1).

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Authors and Affiliations

  1. Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University of Munich, Goethestrasse 33, 80336, Munich, Germany

    Susanna Glas, Stefan Tyroller, Wolfgang Zwickenpflug & Elmar Richter

  2. Merck KGaA, Institute of Drug Metabolism and Pharmakokinetics, Am Feld 32, 85567, Grafing, Germany

    Kurt Steiner & Gudrun Kiefer

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  1. Susanna Glas
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  2. Stefan Tyroller
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  3. Wolfgang Zwickenpflug
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  4. Kurt Steiner
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  5. Gudrun Kiefer
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  6. Elmar Richter
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Correspondence to Stefan Tyroller.

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Glas, S., Tyroller, S., Zwickenpflug, W. et al. Tissue distribution and excretion of myosmine after i.v. administration to Long–Evans rats using quantitative whole-body autoradiography. Arch Toxicol 81, 151–161 (2007). https://doi.org/10.1007/s00204-006-0137-6

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  • DOI: https://doi.org/10.1007/s00204-006-0137-6

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