Parkinson’s Disease & Pesticides: By Dr. Zayd Ratansi

Idiopathic Parkinson’s Disease (PD) and Pesticides: an Argument for Rational Therapy Based on Known Epidemiological Studies.

By Dr. Zayd Ratansi, ND

Although by strict criteria, the etiology of Parkinson’s Disease (PD) is still considered idiopathic, one cannot ignore the very large body of epidemiological evidence linking long term herbicide, fungicide and pesticide exposure to the pathogenesis of Parkinson’s disease. Dozens of studies using 1-methyl-4-phenylpyridinium (MPTP) and Rotenone, both herbicide analogues, have helped to elucidate the biological cascade that leads to selective cell death of dopaminergic neurons of the substantia nigra of PD patients. Present day treatment of this refractory neurological disease consists mainly of replacement of dopamine through decarboxylation of levodopa, and promotion of its uptake through the BBB by peripheral inhibition of this conversion by carbidopa. Other approaches have included slowing the breakdown of dopamine by MAO inhibition through the use of Deprenyl (Selegiline), and inhibiting glutamate (excitatory neurotransmitter) induced neuronal apoptosis through NMDA receptor antagonists. A couple of common themes that these well accepted treatments share are a significant amount of side effects, and the fact that they highly concentrate on curtailing the end products of the Parkinsonian biochemical inhibition, replacing dopamine and avoiding oxidative neuronal cell destruction. These are logical treatment strategies and necessary for preventing the patients’ clinical decompensation. However, reviewing the medical literature and a good number in vivo and in vitro studies, it is clear that many safe, intermediary natural interventions exist to prevent the initial loss of dopamine (DA) neurons in the first place. The rest of this paper will focus on some of these interventions. One of the main focuses of the paper will be considering the hypothesis that PD may be linked to pesticide exposure and that treating the causative factor with detoxification regimens can lead to long lasting clinical improvement in Parkinson’s patients.

First, a quick review of the biochemical defects postulated to underlie PD. It is agreed that the main pathogenic defects center along the function of the mitochondrial complex I of the electron transport chain in the DA cells of the substantia nigra. In normal function, extra cellular NADH reduces FMN. The reduced FMNH2 transfers a pair of electrons to a series of between 6-8 Iron sulfur (thiol) centers; the final result is the reduction of Ubiqinone or Coenzyme Q10. Down through another major series of steps and through complex 3 results in the oxidative phosporylation of ATP. (Biochemistry, Mckee). It is postulated that, pesticides, herbicides and fungicides, analogues of MPTP/MPP+ can start the process of DA substantia nigra apoptosis by binding to NADH dehydrogenase multienzyme complex [1]. The process of neuromelination or the auto oxidation of DA cells [2]occurs presumably when these iron sulfur centers, failing to be reduced by FMNH2, start to accumulate [3]. The highly neurotoxic byproducts of the inhibition of the ferredoxin-thioredoxin system and the iron/melanin interaction: hydrogen peroxide (H2O2), and nitrous oxide (NO) [4] [5] [6], rapidly depletes glutathione reductase to its oxidized form of GSSG [7] [8]. Gamma GT/dipeptidase hydrolyses GSSG to its constituent amino acids: glutamate, glycine and cysteine [9]. The severe rise in excitatory glutamate levels in addition to the above mentioned reactive oxygen species (ROS) lead to further formation of highly neurotoxic peroxynitrite (ONOO-) and hydroxyl radicals (OH-) [10] causing lipid peroxidation and subsequent cell death of DA neurons in the striatum and substantia nigra [11].

Next, is the implication of pesticides, herbicides and fungicides involved in the etiological pathogenesis of PD? Numerous retrospective studies have been done showing a very high correlation between Parkinsonian incidence and rural living, pesticide exposure, drinking from well water (presumably contaminated from pesticide soil run off) [12] [13] [14-16] [17-19]. Furthermore, postmortem double blind studies of PD patients have detected selectively high quantities of Dieldrin, hexachlorocyclohexane (lindane), PCB’s, and DDE in PD tissues [20] [21]. Animal studies have confirmed that the well-known fungicide Paraquat directly causes DA cell death:

“The data indicate that paraquat like MPTP elicits a dose-dependent decrease in substantia nigra dopaminergic neurons assessed by a Fluoro-gold prelabeling method, a decline in striatal dopamine nerve terminal density assessed by measurement of tyrosine hydroxylase immunoreactivity; and neurobehavioral syndrome characterized by reduced ambulatory activity. Taken together, these data suggest that systemically absorbed paraquat crosses the blood- brain barrier to cause destruction of dopamine neurons in the substantia nigra, consequent reduction of dopaminergic innervation of the striatum and a neurobehavioral syndrome similar to the well characterized and bona fide dopaminergic toxin MPTP.” [22]

A study showed the combined effects of herbicides: paraquat and Maneb had synergistic effects in inhibiting nigrostriatal dopamine systems in a study with mice [23].

One study concluded that ongoing depletion of GSH implied the continued local presence of a (xenobiotic) neurotoxin [24]. Environmental studies in Israel have confirmed abundant pesticide traces of carbamates and organophosphates in areas where there were unusually high incidence of PD and preparkinsonian symptoms [25]. Systemic ability to breakdown hydrogen peroxide, also elevated in the substantia nigra of PD, was compromised by the inhibition of superoxide dismutase (SOD) through the administration of the herbicides MCPA and Aniten I in an animal study [26].

This is not to imply that PD has solely, exogenous causative determinants. Many of the epidemiological studies show that family history is the most highly correlated risk factor for the development of Parkinson’s disease. [16, 17]. One could hypothesize from a quick review of the literature, that a combined ecogenetic factors are both necessary for the development of PD. This is evidenced by the different polymorphisms of GSTP1-1 and CYP2D6 genes that can make individuals more susceptible to quicker GSH depletion and problems with xenobiotic metabolism[17, 27]. In other words, both hereditary susceptibility and mild environmental exposure or just frequent and intense exposure till GSH systems are overwhelmed are required for PD development. This is consistent with the epidemiological studies.

In addition to pesticides, heavy metal exposure can be another compounding environmental factor in the development of PD, specifically: iron, copper, and manganese [28-30]. Manganese (Mn++) and Iron (Fe++/+++) both catalyze the auto oxidation of dopamine. They do this by there production of hydroxyl and cysteine derived thyl radicals [6]. These reactions have been confirmed in vitro [31]. Manganese toxicity can occur as a result of exhaust fumes from the antiknock, fuel additive Methylcyclopenadienyl Mn tricarbonyl (MMT). While iron overload, hemochromotosis, can be due to genetic HLA markers that predispose to increased Fe++ absorption, dietary iron overload, sideroblastic anemia, occupational exposure, and iron supplementation (Robbins, Pathologic basis of disease).

The aforementioned review of PD development will now serve as background for the rational for the predopaminergic cell death natural interventions presented hereafter. These interventions are stressed because the current medical literature supports their promise, they are preventative in the sense that they preserve the integrity of the substantia nigra rather than focus on replacing dopamine, and they are by and large, non-toxic. L-dopa itself, the mainstay treatment for PD, has been shown to increase free radical production, which is ameliorated by high dose antioxidants [32]. The limitations of these natural interventions must also be stressed in that they do not treat the actual cause of the disease if indeed Parkinson’s has an ecogenetic etiology. This would be better addressed by environmental medicine and medical genetics. The former will also be discussed and considered in this paper in the scope of natural treatment for PD.

One natural way to overcome the mitochondrial respiratory compromise in PD is to overcome its deficits through mass action of respiratory chain inducers. Two substances with this ability that have been studied are Nicotine Adenine Dinucleotide (NADH) and Acetyl-L Carnitine. NADH can stimulate the natural production of Levodopa via its activation of tyrosine hydroxylase (TH), the rate limiting enzyme in levodopa production [33]. Birkmayer et al has demonstrated both clinical and objective improvements in PD patients in both large and small open trials using IV NADH [34, 35]. Acetyl-L-Carnitine, by its ability to cross mitochondrial membranes and supply precursor to pyruvate to the Krebs cycle has also been postulated to aid in PD. Acyl L- Carnitine has been shown to protect DA neurons from MPTP induced cytotoxicity [36] and showed clinical improvement in aiding PD patients in sleeping and ambulation [37].

The literature has seemingly reached a consensus that the neuronal cell death in PD is due to oxidatative stress. In particular, GSH depletion has been targeted as the source of this increased oxidative stress [8, 38]. Many studies have focused on the repletion of GSH as a means to prevent the oxidative death of DA neuronal cells. This accomplished in a variety of ways. First, there is direct GSH IM or IV replacement. Sechi et al. demonstrated clinical improvement in all PD patients in a small study of infusion of IV GSH [39, 40]. The same results were shown in an in vivo animal study involving rat brains [41]. A second, seemingly equally effective way to increase GSH concentration is through the administration of GSH precursors: Selenium, and specifically N-acetylcysteine (NAC). NAC provides the sulfhydyl groups in the iron sulfur centers of mitochondrial complex I in addition to being a GSH precursor [42] Offen et al, in a animal study, demonstrated the protective effect of NAC, GSH and other thiol containing compounds against nigrostriatal apoptosis [43]. In another study, Martinez Banaclocha demonstrated that NAC maximized mitochondrial complex I activity in aging mice [44]. In a recent human trial by De Rosa et al, NAC demonstrated a direct unequivocal increase in GSH levels of HIV patients [45]. Selenium showed in vivo increases in both SOD and GSH and protected against Amphetamine induced nigrostriatal toxicity in a study of mice [46].

One other very practical way to increase intracellular GSH is through the intake of dietary or supplementary cruciferous vegetables, which contain a natural abundance of thiol groups. The efficacy of this approach has also been shown in vivo studies [47] [48]. Vitamin D3, cholecalciferol has also been purported to enhance the intracellular GSH concentration in the CNS [49].

A third, indirect way of enacting nigrostriatal protection is to supplement with other antioxidants shown to protect these cells from ROS. Melatonin and Vitamin C have been shown to be potent neurological antioxidants. Melatonin quenches the free radicals of literally all the known ROS active in PD: hydroxyl radicals, superoxide anions, peroxynitrite, and peroxyl radicals. In addition to these scavenging effects, melatonin also inhibits nitric oxide synthase and stimulate mRNA for SOD, glutathione peroxidase and glutathione reductase. Melatonin, in vivo and in vitro studies, has been shown prophylactically to reduce oxidative damage in several models of Parkinson’s disease (dopamine auto-oxidation, 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine and 6-hydroxydopamine), and to protect against glutamate excitotoxicity. [50]. [51]. Vitamin C has been shown to inactivate DA quinones, which are severely neurotoxic [2].

Another method for the prevention of nigrostriatal cell death in PD is to remove the inducers of ROS, mainly heavy metals, especially if they are detected to be elevated in RBC, UA or ferritin labs. The traditional treatment for this is heavy metal chelation with DMSA, DMPS, BAL or Deferoxamine for iron overload. Rat studies with Deferoxamine prevented the 6-OHDA induced loss of dopamine [4]. In another animal study, deferoxamine allowed the survival of MPTP poisoned rats while all of the control animals died [52].

Finally, if PD has such great correlation with environmental exposure, and these xenobiotics can accumulate and store in the adipose, liver, and CNS, the most rational top down approach aiming at a causal intervention involves active detoxification. Conventional medicine uses hemodialysis for acute poisonings, but this will only clear extracellular blood and not toxins stored intracellularly in adipose, CNS and liver. If PD patients show labs or history indicating herbicide, pesticide, fungicide or heavy metal exposure, a simple, natural, active detoxification regimen has been shown to be the most effective method for clearance of stored xenobiotics. The regimen that has been repeatedly shown to be effective in the literature is known as the Hubbard method. It is a natural regimen designed to alter the metabolism and to increase excretion of xenobiotics through the body’s 5 natural organs of detoxification and excretion: the liver, the kidneys, the lungs, the bowels and the skin. The program consists of the following given in a 3 week regimen:

PUFA EFA Supplement.
Daily aerobic exercise. 30 minutes –1 hour/day
½ hr. sauna at 60-82 degrees C
Vitamin and mineral support centered around gradually increasing nicotinic acid levels
Cal/Mag supplement.
Filtered water and electrolyte replacement.
Orderly schedule with light, easily digested organically grown foods.
Adequate sleep.
No medications, ETOH or recreational drugs during the regimen unless specifically prescribed by the Physician.

Also specific to detoxification and PD, dietary restriction or short periods of clinical fasting were found to be detoxifying and reducing to oxidative stress in animal induced models of PD [53].

This method was found to be safe with no side effects in a previous study with 103 individuals [54]. These are some of the results found studies utilizing Hubbard detoxification regimen:

A study of seven individuals was evaluated pre and post treatment for the removal of 16 organohalides through the Hubbard detoxification method. 10 of the 16 measured pesticides showed significantly significant reduction at 1 and 4 mos. post treatment. There was no evidence of redistribution of toxins into different bodily compartments [54].
In a case study of 23 yr old woman who had pesticide exposure, the Hubbard technique was prescribed and the physicians noted black substance being excreted by the sebaceous glands and sweat which was later identified as PCB’s. The removal of the toxic substance was accompanied by the remission of her subjective complaints. [55]
In a controlled study of electrical workers exposed to Hexochlorobenzene, PCB’s, Deildrin, oxychlordane, heptachlor epoxide and dichlorophenyldichloroethylene, the Hubbard method was used to detoxify the experimental group while the control group received no treatment. At post treatment, all chemicals were significantly lowered in concentration in the treatment group, while most chemicals were insignificantly higher in the control group. Symptom scores greatly improved in the treatment group, while they stayed the same or worsened in the controls. [56]
In a study of the general physiological effects, safety and clinical improvement of a detoxification regimen for the removal of adipose stored xenobiotics, the regimen was found to be safe and well tolerated by environmental patients exposed to recreational and iatragenically induced drug toxicity, occupational, and environmental exposures. Patients with high blood pressure had a mean reduction of 30.8 mm systolic and 23.3 mm diastolic. Cholesterol level mean reduction was 19.5 mg/100ml. The program resulted in improvements of Psychological and IQ test scores. There was also a plethora of clinical symptom improvement in 70% of all cases. [57]
In a clinical study of symptomatic capacitor workers exposed to PCB’s on the job, the Hubbard detoxification protocol brought about a mean reduction of adipose tissue PCB’s of 37.4 mg/kg and in serum by 261 ug, a 63% and 49% reduction respectively. 90% of reported symptoms ceased after the treatment. Excretion of intact PCB’s in sebum was increased 5 fold during detoxification. [58]
Another case study of 33 yr. old Vietnam vet who had a history of dioxin exposure also tested positive for DDE and PCB’s. He was placed on a detoxification protocol and experienced full resolution of symptoms. Adipose levels of both DDE and PCB fell appreciably. [59]
The Hubbard detoxification method was used in a study of Cocaine addicts in an attempt to detoxify their systems. Cocaine was found both in the sweat and urine of the subjects during the study. Low levels continued to be excreted for several weeks after the regimen. [60]
In the Healthmed study of chemically exposed workers undergoing a detoxification protocol the symptoms reported pre and post treatment were as follows: [61]

Symptom	% of pretreatment group	% of post treatment group
Rash	18	4%
Acne	16	4
Skin thickening	9	4
Parathesias	14	2
Weakness	16	4
Uncoordination	7	0
Dizziness	18	2
Fatigue	79	5
Nervousness	14	4
Disorientation	11	0
Headaches	40	9
Joint Pain	5	0
Muscle pain	42	5
Abdominal Pain	33	11
Constipation	26	2

In conclusion, PD can be seen as having a multifactorial etiology with epidemiological evidence leaning toward hereditary and environmental causes. Through the biochemistry, it is evident that present day treatments, albeit very sophisticated in pharmacology and biochemistry are simply treating the symptoms of this dreaded neurological disease. As elucidated, there are a number of natural substances including: glutathione, NAC, Acyl-L-Carnitine, Vitamin C and heavy metal chelators that can prevent the dopaminergic cell death and clinical decompensation. Furthermore, a strong argument is made for intervention at the causal level of PD by the simple, safe, and effective method of detoxification demonstrated in the scientific literature. HOC Centers for Progressive Health has developed an even more sophisticated system of detoxification utilizing the latest in modern technology and comfort. (Please see attached detoxification Protocol). It is our hope to further the scientific inquiry into the etiology of chronic degenerative disease including PD and to lessen the suffering or cure those afflicted with this malady. Thank you for your consideration of our progressive hypothesis of PD. Your critique, input and expertise are welcome.

1. Kashiwaya, Y., et al., D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc Natl Acad Sci U S A, 2000. 97(10): p. 5440-4.

2. Drukarch, B. and F.L. van Muiswinkel, Drug treatment of Parkinson’s disease. Time for phase II. Biochem Pharmacol, 2000. 59(9): p. 1023-31.

3. Jellinger, K.A., The role of iron in neurodegeneration: prospects for pharmacotherapy of Parkinson’s disease. Drugs Aging, 1999. 14(2): p. 115-40.

4. Ben-Shachar, D., et al., Role of iron and iron chelation in dopaminergic-induced neurodegeneration: implication for Parkinson’s disease. Ann Neurol, 1992. 32(Suppl): p. S105-10.

5. McNaught, K.S. and P. Jenner, Extracellular accumulation of nitric oxide, hydrogen peroxide, and glutamate in astrocytic cultures following glutathione depletion, complex I inhibition, and/or lipopolysaccharide-induced activation. Biochem Pharmacol, 2000. 60(7): p. 979-88.

6. Shen, X.M. and G. Dryhurst, Iron- and manganese-catalyzed autoxidation of dopamine in the presence of L-cysteine: possible insights into iron- and manganese-mediated dopaminergic neurotoxicity. Chem Res Toxicol, 1998. 11(7): p. 824-37.

7. Pearce, R.K., et al., Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease. J Neural Transm, 1997. 104(6-7): p. 661-77.

8. Nicole, A., D. Santiard-Baron, and I. Ceballos-Picot, Direct evidence for glutathione as mediator of apoptosis in neuronal cells. Biomed Pharmacother, 1998. 52(9): p. 349-55.

9. Han, J., et al., Inhibitors of mitochondrial respiration, iron (II), and hydroxyl radical evoke release and extracellular hydrolysis of glutathione in rat striatum and substantia nigra: potential implications to Parkinson’s disease. J Neurochem, 1999. 73(4): p. 1683-95.

10. Marshall, K.A., et al., The neuronal toxicity of sulfite plus peroxynitrite is enhanced by glutathione depletion: implications for Parkinson’s disease. Free Radic Biol Med, 1999. 27(5-6): p. 515-20.

11. Li, Y., P. Maher, and D. Schubert, Requirement for cGMP in nerve cell death caused by glutathione depletion. J Cell Biol, 1997. 139(5): p. 1317-24.

12. Marder, K., et al., Environmental risk factors for Parkinson’s disease in an urban multiethnic community. Neurology, 1998. 50(1): p. 279-81.

13. Semchuk, K.M., E.J. Love, and R.G. Lee, Parkinson’s disease and exposure to agricultural work and pesticide chemicals. Neurology, 1992. 42(7): p. 1328-35.

14. Fall, P.A., et al., Nutritional and occupational factors influencing the risk of Parkinson’s disease: a case-control study in southeastern Sweden. Mov Disord, 1999. 14(1): p. 28-37.

15. Baldi, I., et al., [Delayed health effects of pesticides: review of current epidemiological knowledge]. Rev Epidemiol Sante Publique, 1998. 46(2): p. 134-42.

16. Barbeau, A., et al., Ecogenetics of Parkinson’s disease: prevalence and environmental aspects in rural areas. Can J Neurol Sci, 1987. 14(1): p. 36-41.

17. Chan, D.K., et al., Genetic and environmental risk factors for Parkinson’s disease in a Chinese population. J Neurol Neurosurg Psychiatry, 1998. 65(5): p. 781-4.

18. Gorell, J.M., et al., The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology, 1998. 50(5): p. 1346-50.

19. Priyadarshi, A., et al., A meta-analysis of Parkinson’s disease and exposure to pesticides [In Process Citation]. Neurotoxicology, 2000. 21(4): p. 435-40.

20. Corrigan, F.M., et al., Organochlorine insecticides in substantia nigra in Parkinson’s disease. J Toxicol Environ Health, 2000. 59(4): p. 229-34.

21. Fleming, L., et al., Parkinson’s disease and brain levels of organochlorine pesticides. Ann Neurol, 1994. 36(1): p. 100-3.

22. Brooks, A.I., et al., Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res, 1999. 823(1-2): p. 1-10.

23. Thiruchelvam, M., et al., Potentiated and preferential effects of combined paraquat and maneb on nigrostriatal dopamine systems: environmental risk factors for Parkinson’s disease? Brain Res, 2000. 873(2): p. 225-34.

24. Perry, T.L. and V.W. Yong, Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett, 1986. 67(3): p. 269-74.

25. Herishanu, Y.O., E. Kordysh, and J.R. Goldsmith, A case-referent study of extrapyramidal signs (preparkinsonism) in rural communities of Israel. Can J Neurol Sci, 1998. 25(2): p. 127-33.

26. Holovska, K., et al., Antioxidant and detoxifying enzymes in the liver and kidney of pheasants after intoxication by herbicides MCPA and ANITEN I. J Biochem Mol Toxicol, 1998. 12(4): p. 235-44.

27. Menegon, A., et al., Parkinson’s disease, pesticides, and glutathione transferase polymorphisms [see comments]. Lancet, 1998. 352(9137): p. 1344-6.

28. Gorell, J.M., et al., Occupational exposures to metals as risk factors for Parkinson’s disease. Neurology, 1997. 48(3): p. 650-8.

29. Gorell, J.M., et al., Occupational exposure to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson’s disease. Neurotoxicology, 1999. 20(2-3): p. 239-47.

30. Gorell, J.M., et al., Occupational metal exposures and the risk of Parkinson’s disease. Neuroepidemiology, 1999. 18(6): p. 303-8.

31. Lloyd, R.V., Mechanism of the manganese-catalyzed autoxidation of dopamine. Chem Res Toxicol, 1995. 8(1): p. 111-6.

32. Prasad, K.N., W.C. Cole, and B. Kumar, Multiple antioxidants in the prevention and treatment of Parkinson’s disease. J Am Coll Nutr, 1999. 18(5): p. 413-23.

33. Kuhn, W., et al., Parenteral application of NADH in Parkinson’s disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis. J Neural Transm, 1996. 103(10): p. 1187-93.

34. Birkmayer, W. and G.J. Birkmayer, Nicotinamidadenindinucleotide (NADH): the new approach in the therapy of Parkinson’s disease. Ann Clin Lab Sci, 1989. 19(1): p. 38-43.

35. Birkmayer, J.G., et al., Nicotinamide adenine dinucleotide (NADH)–a new therapeutic approach to Parkinson’s disease. Comparison of oral and parenteral application. Acta Neurol Scand Suppl, 1993. 146: p. 32-5.

36. Bodis-Wollner, I., et al., Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates. J Neural Transm Park Dis Dement Sect, 1991. 3(1): p. 63-72.

37. Puca, F.M., et al., Clinical pharmacodynamics of acetyl-L-carnitine in patients with Parkinson’s disease. Int J Clin Pharmacol Res, 1990. 10(1-2): p. 139-43.

38. Lan, J. and D.H. Jiang, Excessive iron accumulation in the brain: a possible potential risk of neurodegeneration in Parkinson’s disease. J Neural Transm, 1997. 104(6-7): p. 649-60.

39. Sechi, G., et al., Reduced intravenous glutathione in the treatment of early Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry, 1996. 20(7): p. 1159-70.

40. Calabrese, V., et al., Cysteine-induced enhancement of lipid peroxidation in substantia nigra: comparative effect with exogenous administration of reduced glutathione. Drugs Exp Clin Res, 1997. 23(1): p. 25-31.

41. Pocernich, C.B., M. La Fontaine, and D.A. Butterfield, In-vivo glutathione elevation protects against hydroxyl free radical- induced protein oxidation in rat brain. Neurochem Int, 2000. 36(3): p. 185-91.

42. Martinez, M., et al., Hypothesis: can N-acetylcysteine be beneficial in Parkinson’s disease? Life Sci, 1999. 64(15): p. 1253-7.

43. Offen, D., et al., Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson’s disease. Exp Neurol, 1996. 141(1): p. 32-9.

44. Martinez Banaclocha, M., N-acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice: implications for treatment of Parkinson’s disease. Brain Res, 2000. 859(1): p. 173-5.

45. De Rosa, S.C., et al., N-acetylcysteine replenishes glutathione in HIV infection [In Process Citation]. Eur J Clin Invest, 2000. 30(10): p. 915-29.

46. Kim, H.C., et al., Protection of methamphetamine nigrostriatal toxicity by dietary selenium. Brain Res, 1999. 851(1-2): p. 76-86.

47. Clapper, M.L., et al., Preclinical and clinical evaluation of broccoli supplements as inducers of glutathione S-transferase activity. Clin Cancer Res, 1997. 3(1): p. 25-30.

48. Nijhoff, W.A., et al., Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans. Carcinogenesis, 1995. 16(9): p. 2125-8.

49. Shinpo, K., et al., Effect of 1,25-dihydroxyvitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine. J Neurosci Res, 2000. 62(3): p. 374-382.

50. Reiter, R.J., Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol, 1998. 56(3): p. 359-84.

51. Jin, B.K., et al., Melatonin protects nigral dopaminergic neurons from 1-methyl-4- phenylpyridinium (MPP+) neurotoxicity in rats. Neurosci Lett, 1998. 245(2): p. 61-4.

52. van Asbeck, B.S., et al., Continuous intravenous infusion of deferoxamine reduces mortality by paraquat in vitamin E-deficient rats. Am Rev Respir Dis, 1989. 139(3): p. 769-73.

53. Duan, W. and M.P. Mattson, Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease. J Neurosci Res, 1999. 57(2): p. 195-206.

54. Schnare, D.W., et al., Reduction of Human Organohalide Body Burdens: Final Research Report. 1983, Foundation for Advancements in Science and Education: Los Angeles, Ca. p. 1-16.

55. Root, D. and G. Lionelli, Excretion of a Lipophilic Toxicant through the Sebaceous Glands: a Case report. J. Toxic.-Cut &Ocular Toxic., 1987. 6((1)): p. 13-17.

56. Schnare, D. and P. Robinson. Hexachlorobenzene:Proceedings of an International Symposium. in International Agency for Research on Cancer, Lyon. 1985. Lyon, France: IARC Scientific Publications.

57. Schnare, D.W., et al., Evaluation of a detoxification regimen for fat stored xenobiotics. Med Hypotheses, 1982. 9(3): p. 265-82.

58. Tretjak, Z., M. Shields, and S.L. Beckmann, PCB reduction and clinical improvement by detoxification: an unexploited approach? Hum Exp Toxicol, 1990. 9(4): p. 235-44.

59. Roehm, D., Effects of a program of Sauna Baths and Megavitamins on Adipose DDE and PCB’s and on Clearing of Symptoms of Agent Orange (dioxin) Toxicity. Clinical Research, 1983. 31(2): p. 243A.

60. Addressing the Human Costs of Chemical Contamination. 1995, FASE Research Report. p. 1-3.

61. Root, D. and J. Anderson, Reducing Toxic Body Burdens Advancing in Innovative Technique. Occupational Health and Safety News Digest, 1986. 2(4): p. 1-4.

Name:
Email: