Modulating NSAID cytotoxicity by inhibiting or inducing glucuronidation
Subtitle: a QSTR study.
Published: 2004
Language: eng
Number of pages: 75
Description: QSTR analysis showed that NSAID cytotoxicity increased as their logP increased. The cytotoxicity of some NSAIDs was also determined by their pKa. NSAID hydrophobicity also determined the ease of glucuronidation.The aim of this work was to investigate the effect of inhibiting nonsteroidal anti-inflammatory drugs (NSAID) glucuronidation on NSAID-induced cytotoxicity and develop a quantitative structure-toxicity relationship (QSTR) model using non-specific physicochemical parameters, hydrophobicity (loge) and ionization constant (pKa), for NSAIDs cytotoxicity.For most NSAIDs P450 metabolism is an activation pathway, resulting in the production of toxic metabolites.The NSAID susceptibility of control isolated hepatocytes was compared with uridine diphosphoglucuronosyl transferase (UGT) induced hepatocytes (using phenobarbital or 3-methylcholanthrene) and UGT inactivated hepatocytes. Even though, the formation of reactive acyl glucuronide intermediates is thought by other investigators to contribute to the toxicity of NSAIDs, UGT induced hepatocytes were more resistant to most NSAIDs and UGT inhibited hepatocytes were more susceptible.
Notes: Adviser:  P. J. O'Brien.

Thesis (M.Sc.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Masters Abstracts International, Volume: 42-06, page: 2178.

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