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.
The NO/ONOO- cycle
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 (Chiara De Luca, et al.) is significant in regard to the NO/ONOO- cycle theory because it shows that three elements of the cycle are elevated in MCS patients. [Their report – “Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes” – was published online April 27 by the journal Toxicology and Applied Pharmacology.
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 in MCS 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.”
Martin L. Pall, PhD
Professor Emeritus of Biochemistry and Basic Medical Sciences
Washington State University
Source: Martin L Pall/Washington State University, press release, Jul 5, 2010
Note: Asked if he would have more news for us, Dr. Pall replied “There will always be more.”