Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

The metabolism of isometamidium in hepatocytes from control and inducer treated rats

Boibessot, I. and Tettey, J.N.A. and Skellern, G.G. and Watson, D.G. and Grant, M.H. (2006) The metabolism of isometamidium in hepatocytes from control and inducer treated rats. Journal of Veterinary Pharmacology and Therapeutics, 29 (6). pp. 547-553. ISSN 0140-7783

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

Little is known about the metabolism and mechanism of action of the trypanocide, isometamidium (ISM), the major drug used for prophylaxis of trypanosomiasis. We have investigated its metabolism and distribution in isolated rat hepatocytes using liquid chromatography-mass spectrometry and confocal laser scanning microscopy (CLSM). Two putative metabolites were formed, which were proposed to be a mono-acetyl derivative and an oxidized metabolite (SII). This is the first demonstration of the hepatic metabolism of ISM, as previous in vivo studies were hampered by dose-limiting toxicity and insensitive analytical methods. The intrinsic fluorescence of the drug enabled its intracellular uptake to be followed by CLSM. It is taken up rapidly into the nucleolus, nuclear membrane and endoplasmic reticulum within 5 min, and retained in the nucleus for at least 24 h. Persistent binding of ISM to cellular macromolecules may contribute to its prophylactic effect in vivo. Pretreatment of rats with 3-methylcholanthrene, phenobarbitone (PB) or the widely used pyrethroid pesticide, deltamethrin, resulted in an increase in metabolism of ISM to the proposed SII after 1 h incubation with hepatocytes. 3-methylcholanthrene was the most potent inducer, causing a maximal 19.5-fold induction of SII formation after exposure of hepatocytes to ISM for 1 h compared with formation by control hepatocytes. In comparison, at the 1 h timepoint deltamethrin pre-treatment caused a 10.2-fold induction, and PB only 8.2 fold.

Item type: Article
ID code: 28464
Keywords: metabolism , trypanocide, isometamidium metabolism, trypanosomiasis, rat hepatocytes , Bioengineering, Engineering (General). Civil engineering (General), veterinary(all), Pharmacology
Subjects: Technology > Engineering (General). Civil engineering (General) > Bioengineering
Technology > Engineering (General). Civil engineering (General)
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Engineering > Bioengineering
Related URLs:
    Depositing user: Ms Ashley Urie
    Date Deposited: 27 Jul 2011 14:31
    Last modified: 05 Sep 2014 04:45
    URI: http://strathprints.strath.ac.uk/id/eprint/28464

    Actions (login required)

    View Item