Organochlorine Insecticides in Substantia Nigra in Parkinson's Disease

Abstract

The concentrations of organochlorine (OC) compounds in the substantia nigra (SN) were compared in Parkinson's disease (PD) with concentrations in brain from cortical Lewy body dementia (CLBD), Alzheimer's disease (AD), and nondemented nonparkinsonian controls (CON). The levels of the gamma isomer of hexachlorocyclohexane (gammaHCH, lindane) were significantly higher in PD tissues (mean +/- SD: 0.56 +/- 0.434 microg/g lipid) than in the other three groups (CLBD 0.052 +/- 0.101 microg/g lipid; AD none detected; CON 0.125 +/- 0.195; all differences from PD significant at p < .05, Mann-Whitney U-test). Dieldrin (HEOD) was higher in PD brain than in AD or control brain, while 1,1'-(2,2-dichloroethenyl diene)-bis(4-chlorobenzene) (p,p-DDE) and total Aroclor-matched polychlorinated biphenyls (matched PCBs) were only higher in PD substantia nigra when these concentrations were compared with those of CLBD. These findings are not inconsistent with the hypothesis derived from epidemiological work and animal studies that organochlorine insecticides produce a direct toxic action on the dopaminergic tracts of the substantia nigra and may contribute to the development of PD in those rendered susceptible by virtue of cytochrome P-450 polymorphism, excessive exposure, or other factors.

The Role of Oxidative Stress in Parkinson's Disease

“…Epidemiologic studies corroborate an association between exposure to pesticides frequently used in agriculture with the increased risk of developing PD [204–207]. Sera from PD patients have higher levels of these substances than controls [204, 205], and organochlorine insecticides are detected at higher levels in the PD substantia nigra than in non-PD brains [208].…”

“…Sera from PD patients have higher levels of these substances than controls [204, 205], and organochlorine insecticides are detected at higher levels in the PD substantia nigra than in non-PD brains [208]. The risk may be increased after exposure to multiple pesticides compared to exposure to any one alone [209, 210].…”

Pesticides and Parkinson’s Disease—Is There a Link?

“…The results presented in these abstracts do not differ significantly from the overall findings from other studies. In addition, we identified three autopsy studies that examined the levels of various pesticides and their metabolites in the brains of PD cases (Corrigan et al 1998, 2000; Fleming et al 1994). The number of cases in the studies ranged from 34 to 496, and the number of controls from 25 to 2,070, although one nested case–control study used the rest of the cohort (22,286) as their controls ( Table S1; http://ehp.niehs.nih.gov/docs/2005/8095/supplemental.pdf).…”

“…Other specific groups of pesticides have also shown positive associations with PD, including organochlorines (Figure 2). Three autopsy case–control studies found increased levels of dieldrin and lindane in the brains of deceased PD patients compared with other diseased brains (Corrigan et al 1998, 2000; Fleming et al 1994). Positive associations were also seen with exposure to organophosphates and carbamates pesticides (Firestone et al 2005; Wechsler et al 1991; data not shown), although in only one study was the association significant (Seidler et al 1996).…”

Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring

“…Research over the last several decades has provided a wealth of support for exposure to environmental chemicals, including organochlorine insecticides as a risk factor for PD (Hatcher et al , 2008). Indeed, levels of organochlorine compounds, such as dieldrin and β-HCH have been found to be elevated in the brain tissue and serum, respectively, of PD patients and have been shown in laboratory studies to damage the nigtrostriatal dopamine system (Corrigan et al , 1996; Corrigan et al , 2000; Kitazawa et al , 2001; Kitazawa et al , 2004; Hatcher et al , 2007; Richardson et al , 2009; Richardson et al , 2011). In addition to these compounds, a recent epidemiological study also identified exposure to the organochlorine insecticide, endosulfan, as a risk factor for PD (Rhodes et al , 2013).…”