Chemical exposures and Parkinson's disease in residents of three Negev kibbutzim.
We consider whether chemical pollutants in drinking water (including aromatic hydrocarbons, alkanes, halogenated aliphatic hydrocarbons, and phthalic acid) or used occupationally in agriculture that have shown no parkinsonism-inducing effect may be responsible for excess cases of Parkinson's disease (PD) in three adjacent kibbutzim in southern Israel (Negev). Literature data on PD pathogenesis have been compared with common pathogenetic pathways to xenobiotics effects; the following neurotoxic mechanisms, besides individual sensitivity, have been suggested: (1) impairment of the protective role of the substantia nigra against toxicants by binding of chemicals to melanin; (2) oxidative stress induction, including glutathione reduction, impaired calcium metabolism, and alteration of cytochrome P-450 activity; (3) blockade of iron chelators because of structural similarities to them or their precursors; (4) mediation of the production of endogenous dopaminergic neurotoxins, such as trichloroharmanes or isoquinolines; (5) blockade of dopamine receptors because of their resemblance to chemicals with affinity to these receptors; (6) stimulation of prostaglandin-H synthase and monooxygenase activity; and (7) stimulation of autoimmune processes and creation of autoimmunity to structures of the dopaminergic system caused by chemical similarity.
Kordysh
E A
EA
Soroka Medical Center, Ben Gurion University of the Negev, Negev, Israel.
Herishanu
Y
Y
Goldsmith
J R
JR
D016573:Agrochemicals / Q000378:metabolism / Q000506:poisoning*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000506:poisoning; D004789:Enzyme Activation; D006801:Humans; D007502:Iron Chelating Agents; D007557:Israel / Q000453:epidemiology; D008543:Melanins / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D018384:Oxidative Stress; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000453:epidemiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000506:poisoning*
D016573:Agrochemicals; D018492:Dopamine Antagonists; D007502:Iron Chelating Agents; D008543:Melanins; D014874:Water Pollutants, Chemical; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases