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Predictions of MCS mechanism confirmed by Italian study
Thursday 8 July 2010
Predictions of Multiple Chemical Sensitivity mechanism confirmed by Roman study
A recent study conducted by a research group in Rome is significant in regard to Martin Pall’s NO/ONOO- cycle theory on Multiple Chemical Sensitivity because it shows that three elements of the cycle are elevated in MCS patients.
Portland, OR – July 5, 2010 – The physiological mechanism for Multiple Chemical Sensitivity proposed by biochemist Martin L. Pall has been confirmed with the recent findings of an independent research group in Rome.
Multiple chemical sensitivity (MCS), also known as chemical sensitivity and toxicant-induced loss of tolerance (TILT), is a disease initiated by toxic chemical exposure, leading to toxic brain injury that produces high level sensitivity to the same set of chemicals that are implicated in initiation of the disease. Sensitivity responses in other areas of the body are also often seen.
“Epidemiological studies show that MCS is a stunningly common disease, even more common than diabetes,” said Pall, professor emeritus of biochemistry and basic medical sciences at Washington State University. “My review of the literature and other research I’ve conducted over the past eleven years shows the probable central mechanism of MCS is a biochemical vicious mechanism, known as the NO/ONOO- cycle.”
Pall’s work is widely published in books and articles, the most recent of which is a chapter in the authoritative international reference manual for professional toxicologists,General and Applied Toxicology, 3rd Edition, 2009 (chapter 92).
The NO/ONOO- cycle, pronounced no-oh-no, is named for the chemical structures of nitric oxide (NO) and peroxynitrite (ONOO-). This biochemical vicious cycle mechanism predicts that each of the elements linked together in the cycle are elevated in patients suffering from MCS and related diseases. Most of the elements of the cycle have been shown to be elevated in such related diseases as chronic fatigue syndrome and fibromyalgia and also in animal models of MCS. However, several cycle elements have never been measured in MCS patients.
The recent study conducted by the research group in Rome is significant in regard to the NO/ONOO- cycle theory because it shows that three elements of the cycle are elevated in MCS patients (De Luca et al, Toxicology and Applied Pharmacology, 2010, April 27 Epub ahead of print). Those elements are the inflammatory cytokines, nitric oxide, and oxidative stress. Each of these measurements provides important confirmation of the disease mechanism proposed by Pall.
The inflammatory cytokines and nitric oxide elevation have never before been measured in MCS patients, although they have been shown to be elevated in animal models of MCS. Oxidative stress has been reported in two earlier studies of MCS patients, but the data provided in the De Luca et al study are much more extensive than are the earlier data. Consequently, these new data all provide important confirmation of the NO/ONOO- cycle as the central disease mechanism in MCS.
The NO/ONOO- cycle also is useful in understanding the role of toxic chemicals in MCS and the role of treatment. Each of the seven classes of chemicals implicated are thought to act indirectly to increase the activity of the NMDA receptors, which are glutamate receptors for controlling synaptic plasticity and memory function. This activity, in turn, leads to rapid increases in intracellular calcium (Ca2+), nitric oxide and peroxynitrite (ONOO-), acting to greatly stimulate the NO/ONOO- cycle.
“Many of the agents used by environmental medicine physicians to treat MCS patients can be viewed as lowering different parts of the cycle, and thus are validated in part by this mechanism,” Pall said. “Consequently, the NO/ONOO- cycle mechanism can be viewed as validating therapeutic approaches used in environmental medicine in the U.S., in Germany and some other areas of Europe and in some other countries.”
Here is the abstract of the Roman study:
PMID: 20430047 [PubMed - as supplied by publisher]
1: Toxicol Appl Pharmacol. 2010 Apr 26; [Epub ahead of print]
Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes.
De Luca C, Scordo MG, Cesareo E, Pastore S, Mariani S, Maiani G, Stancato A, Loreti B, Valacchi G, Lubrano C, Raskovic D, De Padova L, Genovesi G, Korkina LG.
Laboratory of Tissue Engineering & Skin Pathophysiology, Dermatology Institute (IDI IRCCS), Rome, Italy.
BACKGROUND: Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I / phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined.
OBJECTIVES: We sought for genetic, immunological, and metabolic markers in MCS.
METHODS: We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy control&n bsp;s for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined.
RESULTS: Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased.
CONCLUSIONS: Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS. Copyright (c) 2010.
The article originally appeared here.
The news was also reported on the American Chronicle website.
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