Picture offshore wind farm

Open Access: World leading research into plasma physics...

Strathprints makes available scholarly Open Access content by researchers in the Department of Physics, including those researching plasma physics.

Plasma physics explores the '4th' state of matter known as 'plasma'. Profound new insights are being made by Strathclyde researchers in their attempts to better understand plasma, its behaviour and applications. Areas of focus include plasma wave propagation, non-linear wave interactions in the ionosphere, magnetospheric cyclotron instabilities, the parametric instabilities in plasmas, and much more.

Based on the REF 2014 GPA Scores, Times Higher Education ranked Strathclyde as number one in the UK for physics research.

Explore Open Access plasma physics research and of the Department of Physics more generally. Or explore all of Strathclyde's Open Access research...

Formation and protein binding of the acyl glucuronide of a leukotriene b4 antagonist (sb-209247) relation to species differences in hepatotoxicity

Kenny, J.R. and Maggs, J.L. and Tettey, J.N.A. and Harrell, A.W. and Parker, S.G. and Clarke, S.E. and Park, B.K. (2005) Formation and protein binding of the acyl glucuronide of a leukotriene b4 antagonist (sb-209247) relation to species differences in hepatotoxicity. Drug Metabolism and Disposition, 33 (2). pp. 271-281. ISSN 1521-009X

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

Abstract

SB-209247 [(E)-3-[6-[[(2,6-dichlorophenyl)-thio]methyl]-3-(2-phenylethoxy)-2-pyridinyl]-2-propenoic acid], an anti-inflammatory leukotriene B4 receptor antagonist, was associated in beagle dogs but not male rats with an inflammatory hepatopathy. It also produced a concentration-dependent (10-1000 μM) but equal leakage of enzymes from dog and rat precision-cut liver slices. The hepatic metabolism of SB-209247 was investigated with reference to the formation of reactive acyl glucuronides. [14C]SB-209247 (100 μmol/kg) administered i.v. to anesthetized male rats was eliminated by biliary excretion of the acyl glucuronides of the drug and its sulfoxide. After 5 h, 1.03 ± 0.14% (mean ± S.E.M., n = 4) of the dose was bound irreversibly to liver tissue. The sulfoxide glucuronide underwent pH-dependent rearrangement in bile more rapidly than did the SB-209247 conjugate. [14C]SB-209247 was metabolized by sulfoxidation and glucuronidation in rat and dog hepatocytes, and approximately 1 to 2% of [14C]SB-209247 (100 μM) became irreversibly bound to cellular material. [14C]SB-209247 sulfoxide and glucuronide were the only metabolites produced by dog, rat, and human liver microsomes in the presence of NADPH and UDP-glucuronic acid (UDPGA), respectively. Vmax values for [14C]SB-209247 glucuronidation by dog, rat, and human microsomes were 2.6 ± 0.1, 1.2 ± 0.1, and 0.4 ± 0.0 nmol/min/mg protein, respectively. Hepatic microsomes from all three species catalyzed UDPGA-dependent but not NADPH-dependent irreversible binding of [14C]SB-209247 (100-250 μM) to microsomal protein. Although a reactive acyl glucuronide was formed by microsomes from every species, the binding did not differ between species. Therefore, neither the acute cellular injury nor glucuronidation-driven irreversible protein binding in vitro is predictive of the drug-induced hepatopathy.