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

The toxicity of opiates and their metabolites in HepG2 cells

Jairaj, Mark and Watson, D.G. and Grant, M. Helen and Skellern, G.G. (2003) The toxicity of opiates and their metabolites in HepG2 cells. Chemico-Biological Interactions, 146 (2). pp. 121-129. ISSN 0009-2797

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

Abstract

The toxicity of codeine (C), codeinone (CO), morphine (M), oxycodone (OC), pholcodine (P) and pholcodine-N-oxide (P-NOX) was assessed in HepG2 cells by determining cell viability via the measurement of lactate dehydrogenase (LDH) leakage through the membrane, depletion of reduced glutathione (GSH) and measurement of total protein content. Incubation of C, M, OC, P or P-NOX with HepG2 cells resulted in no significant loss of cell viability, depletion of GSH or decreased total protein content. In contrast, with CO there was a marked depletion of GSH with significant differences from control cells (P<0.05) being detected after as little as 5 min. This effect preceded the loss of cell viability and the decrease in total protein content. To identify the cause of GSH depletion during incubations with CO, the incubation solutions were analysed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Analysis showed that a codeinone-glutathione conjugate (CO-SG) had been formed. This adduct was synthesised and characterised by LC/MS/MS and by nuclear magnetic resonance spectroscopy (NMR). CO-SG was quantified in the incubation solutions using the synthesised standard substance. Results obtained in this study support the hypothesis that the toxicity of CO may be partly due to GSH depletion. The absence of LDH leakage and GSH depletion in the incubations containing C or OC suggests, that the presence of both a double bond at - 7 and an adjoining keto-group in the 6-position are necessary to elicit the toxicity of M analogues with regard to GSH depletion.

Item type: Article
ID code: 38232
Keywords: codeine, codeinone–glutathione conjugate, HepG2 cell, opiates, Pharmacy and materia medica, Toxicology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Engineering > Bioengineering
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 06 Mar 2012 15:33
    Last modified: 04 Sep 2014 19:18
    URI: http://strathprints.strath.ac.uk/id/eprint/38232

    Actions (login required)

    View Item