Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products

Philip Burcham, L.M. Kaminskas, F.R. Fontaine, D.R. Petersen, S.M. Pyke

    Research output: Contribution to journalArticlepeer-review

    93 Citations (Scopus)

    Abstract

    Elevated levels of reactive alpha,beta-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)229-236
    JournalToxicology
    Volume181-182
    DOIs
    Publication statusPublished - 2002

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