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 journalArticle

    87 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

    Fingerprint

    Acrolein
    Aldehydes
    Lipid Peroxidation
    Lipids
    Pharmaceutical Preparations
    Proteins
    Dihydralazine
    Pyridoxamine
    Carnosine
    Hydrazones
    Hydralazine
    Nucleophiles
    Poisons
    Malondialdehyde
    Macromolecules
    Amines
    Toxicity
    Disease Progression
    Hepatocytes
    Tissue

    Cite this

    Burcham, Philip ; Kaminskas, L.M. ; Fontaine, F.R. ; Petersen, D.R. ; Pyke, S.M. / Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products. In: Toxicology. 2002 ; Vol. 181-182. pp. 229-236.
    @article{17815ad6806d4ba9abe2f4709ed541bc,
    title = "Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products",
    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.",
    author = "Philip Burcham and L.M. Kaminskas and F.R. Fontaine and D.R. Petersen and S.M. Pyke",
    year = "2002",
    doi = "10.1016/S0300-483X(02)00287-1",
    language = "English",
    volume = "181-182",
    pages = "229--236",
    journal = "Toxicology",
    issn = "0300-483X",
    publisher = "Elsevier",

    }

    Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products. / Burcham, Philip; Kaminskas, L.M.; Fontaine, F.R.; Petersen, D.R.; Pyke, S.M.

    In: Toxicology, Vol. 181-182, 2002, p. 229-236.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products

    AU - Burcham, Philip

    AU - Kaminskas, L.M.

    AU - Fontaine, F.R.

    AU - Petersen, D.R.

    AU - Pyke, S.M.

    PY - 2002

    Y1 - 2002

    N2 - 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.

    AB - 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.

    U2 - 10.1016/S0300-483X(02)00287-1

    DO - 10.1016/S0300-483X(02)00287-1

    M3 - Article

    VL - 181-182

    SP - 229

    EP - 236

    JO - Toxicology

    JF - Toxicology

    SN - 0300-483X

    ER -