Toxicokinetics of tremorogenic natural products, harmane and harmine, in male sprague-dawley rats

Y. Guan, E. D. Louis, W. Zheng

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Tremorogenic β-carboline alkaloids are present in foodstuffs and beverages. Acute exposure to β-carboline derivatives causes severe tremor; however, the disposition of these dietary contaminants remains unclear. This study was performed to evaluate toxicokinetics of harmane and harmine, two major β-carboline alkaloids, in rats. Blood concentrations of both toxicants were quantified by high-performance liquid chromatography (HPLC). Following an intravenous injection (0.5 mg/kg), the concentration-time profiles of harmane or harmine fit well with a two-compartment model. While both compounds had comparable elimination t1/2β (24 and 26 min for harmane and harmine, respectively), the systemic clearance (CLs) for harmine (103.2 ml/kg/ml) was two times greater than that for harmane (52.2 ml/kg/ml). Accordingly, the area under the blood concentration-time curve (AUC) in harmane-treated rats was 2.7-fold greater than that in harmine-treated rats. Harmine appeared to distribute to tissues better than harmane, with a larger volume of distribution (Vd) (3.9 and 1.6 L/kg for harmine and harmane, respectively). After an oral dose (20 mg/kg), the absolute bioavailability (F) was 19% for harmane and 3% for harmine. Harmane was absorbed more slowly flower Ka), yet more completely (higher Cmax, AUC, and F) than harmine. An oral administration of harmane resulted in blood harmine whose formation accounted for 13% of the ingested harmane, indicating a biotransformation of harmane to harmine. These results suggest that harmane is absorbed into the systemic circulation more completely than harmine. Upon entering the body, harmane can be metabolized to form harmine; the latter may better distribute to the tissue compartment.

Original languageEnglish (US)
Pages (from-to)645-660
Number of pages16
JournalJournal of Toxicology and Environmental Health - Part A
Volume64
Issue number8
DOIs
StatePublished - Dec 21 2001
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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