PMID: 7538189Jan 1, 1995Paper

Rat serum albumin modified by diflunisal acyl glucuronide is immunogenic in rats

Life Sciences
S Worrall, R G Dickinson

Abstract

Acyl glucuronide metabolites of carboxylic acid drugs such as the salicylate derivative diflunisal (DF) have been shown to react with proteins in vitro and in vivo to produce covalent adducts. Such attachment of foreign compounds to endogenous molecules could be associated with toxic and/or immune consequences. In this study we have injected rats with rat serum albumin (RSA) modified (a) by DF using a carbodiimide reagent (-->DF-RSA-I, 4.9 micrograms DF/mg RSA) and (b) by incubation with DF acyl glucuronide (DAG) and its rearrangement isomers (iso-DAG) (-->DF-RSA-II, 0.34 micrograms DF/mg RSA). All of the six rats injected with DF-RSA-I produced antibodies reactive with DF-modified keyhole limpet hemocyanin (KLH), the coating protein used in the ELISA. Three out of six animals injected with DF-RSA-II generated similar antibodies. Cross-reactivity with other non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen and ketoprofen (as the free drugs) was not observed. This study shows that a self protein covalently modified by incubation with DAG and iso-DAG is immunogenic in rats. The data thus support the hypothesis that covalent modification of macromolecules by acyl glucuronide metabolites of acidic drugs in vivo can le...Continue Reading

References

Mar 1, 1991·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J A WattR G Dickinson
Jan 1, 1990·Drug Metabolism Reviews·B K Park, N R Kitteringham
Mar 15, 1990·Biochemical Pharmacology·J A Watt, R G Dickinson
Jan 1, 1988·Annual Review of Pharmacology and Toxicology·L R PohlJ G Kenna
Mar 1, 1986·The Journal of Clinical Investigation·P C SmithL Z Benet
Jan 1, 1995·Nature Medicine·P Z Zia-AmirhosseiniL Z Benet
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A DingL Z Benet

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Citations

Feb 22, 2002·Steroids·Nariyasu ManoJunichi Goto
May 23, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Elisabetta GianazzaIngrid Miller
Nov 1, 1996·Journal of Pharmacological and Toxicological Methods·A R King, R G Dickinson
Jul 20, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Nariyasu ManoJunichi Goto
Jun 26, 2002·Biological & Pharmaceutical Bulletin·Ulrich Kragh-HansenMasaki Otagiri
Sep 11, 2010·Biopharmaceutics & Drug Disposition·Sophie L ReganB Kevin Park
Jul 26, 2002·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Urs A Boelsterli
Jul 4, 2008·Current Opinion in Allergy and Clinical Immunology·Sidonie Nelly LavergneDean John Naisbitt
Apr 23, 2002·Chirality·Rasmus Worm MortensenSteen Honoré Hansen
Jan 28, 2003·Therapeutic Drug Monitoring·Maria ShipkovaEberhard Wieland
Jul 14, 2005·European Journal of Drug Metabolism and Pharmacokinetics·S Güniz KüçükgüzelSevim Rollas
Apr 11, 2003·Chemico-biological Interactions·Mark J Bailey, Ronald G Dickinson

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