Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: An HPLC and ESR study

Authors

  • David T. Dexter,

    1. Parkinson's Disease Society Experimental Research Laboratories, Pharmacology Group, Biomedical Sciences Division, King's College London, London
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  • Anne E. Holley,

    1. Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex
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  • William D. Flitter,

    1. Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex
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  • Trevor F. Slater,

    1. Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex
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  • F. Raymund Wells,

    1. Parkinson's Disease Society Brain Bank, University Department of Clinical Neurology, Institute of Neurology, National Hospital, Queen Square, London, England
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  • Susan E. Daniel,

    1. Parkinson's Disease Society Brain Bank, University Department of Clinical Neurology, Institute of Neurology, National Hospital, Queen Square, London, England
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  • Andrew J. Lees,

    1. Parkinson's Disease Society Brain Bank, University Department of Clinical Neurology, Institute of Neurology, National Hospital, Queen Square, London, England
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  • Professor Peter Jenner,

    Corresponding author
    1. Parkinson's Disease Society Experimental Research Laboratories, Pharmacology Group, Biomedical Sciences Division, King's College London, London
    • Pharmacology Group, Biomedical Sciences Division, King's College London, Manresa Road, London, SW3 6LX, England
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  • C. David Marsden

    1. Parkinson's Disease Society Brain Bank, University Department of Clinical Neurology, Institute of Neurology, National Hospital, Queen Square, London, England
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Abstract

Previous studies examining the involvement of oxidative stress in the substantia nigra in Parkinson's disease have measured terminal products of lipid peroxidation or the function of antioxidant defense systems. We report a more specific early marker of lipid peroxidation, lipid hydroperoxides, in a high-performance liquid chromatography (HPLC) and electron spin resonance (ESR) investigation. HPLC-chemiluminescent detection revealed two classes of lipid hydroperoxides in brain tissue extracts–free fatty acid hydroperoxides and cholesterol lipid hydroperoxides. Only cholesterol lipid hydroperoxides were consistently detected in all tissue extracts. Cholesterol lipid hydroperoxides had a 10-fold increase in the Parkinson's disease substantia nigra compared to control subjects. ESR detection of radical degradation products, including those of lipid hydroperoxides, in nigral homogenates incubated with the spin trap N-t-butyl-α-phenyl nitrone (PBN) showed a marked variation in ESR signal between tissues. Despite the increased levels of lipid hydroperoxides in parkinsonian substantia nigra, there was no overall difference in ESR signal intensity between nigral tissues from controls and from patients with Parkinson's disease. The increased levels of an early component of the peroxidation chain in substantia nigra in Parkinson's disease support the hypothesis of a continuous toxic process involving oxygen radical activity. However, using previously frozen tissue, ESR evidence for increased radical formation could not be demonstrated.

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