Inhibition of human LDL oxidation by the neuroprotective drug l-deprenyl.
L-deprenyl (Selegiline) used in the treatment of Parkinson's and Alzheimer's disease also enhances longevity. Oxidized low density lipoprotein promotes atherosclerosis and is toxic to both vascular and neural tissue. The reported association between vascular dysfunction and neurodegenerative diseases prompted us to investigate the effect of l-deprenyl, a MAO-B inhibitor, on low density lipoprotein (LDL) oxidation. LDL was isolated from freshly collected blood and the kinetics of copper induced oxidation of LDL was monitored continuously by spectrophotometry. Oral administration (10 mg) or in vitro (2.8 to 84 microM) addition of l-deprenyl inhibited oxidation of LDL isolated from healthy men and post-menopausal women. This is the first report demonstrating that the antioxidant action of l-deprenyl may be antiatherogenic and cardioprotective. Such an action could contribute to reported extension of life span associated with long-term administration of the drug. In conjunction with inhibition of LDL oxidation, l-deprenyl is unique in that it demonstrates protective effects on both vascular and neuronal tissue. Prophylactic use of low doses of l-deprenyl may accord protection against vascular and neurodegenerative diseases associated with aging.
Thomas
Tom
T
Woodlands Medical Center, 3150 Tampa Road, Oldsmar, Florida 34677, USA. ayurveda.treatment@verizon.net
Bhavnani
Bhagu R
BR
Thomas
Prem
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D000328:Adult; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D003300:Copper; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology; D012642:Selegiline / Q000494:pharmacology* / Q000627:therapeutic use; D012727:Sex Characteristics
D000975:Antioxidants; D008077:Lipoproteins, LDL; D018696:Neuroprotective Agents; D012642:Selegiline; D003300:Copper