OTHER MITOCHONDRIAL NEUROTOXINS

This is a blog about the effect of mitochondrial neurotoxins on glucocorticoid II receptors. It will mostly be about toxins other than the one that I was exposed to, hexachlorophene. I have addressed that research in related blogs.This is an attempt to raise a broader question. Besides hexachlorophene, don't other mitochondrial neurotoxins (eg trimethyltin) also cause life-long glucocorticoid receptor deficiencies that ,in turn, cause disorders of hypercortisolemia, neuroendocrine type
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To begin with,there is a question of whether hexachlorophene and other
mitochondrial neurotoxins are related to glucocorticoid receptor toxicity. So, first, there are a number of articles that relate hexachlorophene and similar mitochondrial neurotoxins with the one that is the focus of this glucocorticoid receptor toxicity research, trimethyltin.


Xenobiotica. 1985 Aug-Sep;15(8-9):727-33.
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Effects of toxic chemicals on the respiratory activity of cultured mouse neuroblastoma cells.Varnbo I, Peterson A, Walum E.Twenty common toxic chemicals were tested for their ability to inhibit respiratory activity in cultured mouse neuroblastoma C1300 cells, clone 41A3. Pentachlorophenol and hexachlorophene exhibited the properties of uncouplers of oxidative phosphorylation, whereas for KCN, pyridine, 2,5-hexandione, NaAsO2, K2Cr2O7, HgCl2, methylmercury and triethyltin more simple time-courses of inhibition ............ Among the effective compounds, those with well-known neurotoxic properties were the most potent in inhibiting respiration in 41A3 cells.

2: Chem Biol Interact. 1979 Sep;27(1):125-32.
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Effect of organotin compounds and hexachlorophene on brain adenosine cyclic 3',5'-monophosphate metabolism.Leow AC, Towns KM, Leaver DD.The effect of triethyltin (TET), triphenyltin (TPT), hexachlorophene (HCP) and cuprizone on adenosine cyclic 3',5'-monophosphate (cyclic AMP) production in rat brain was examined both in vitro and in vivo. TET and TPT inhibited basal adenylate cyclase activity of brain........ On the basis of these results the inhibition of adenylate cyclase produced by TET in brain homogenates in vitro would not appear to be involved in the development of nervous changes associated with acute TET toxicity, or in the production of progressive brain oedema caused by TET, HCP and cuprizone.PMID: 225045 [PubMed - indexed for MEDLINE]
3: Hum Exp Toxicol. 1991 Nov;10(6):439-44.
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A comparison of spongiosis induced in the brain by hexachlorophene, cuprizone and triethyl tin in the Sprague-Dawley rat.Purves DC, Garrod IJ, Dayan AD.DH Department of Toxicology, St Bartholomew's Hospital Medical College, London, UK.The effect of hexachlorophene (HCP; 2,2'-methylenebis(3,4,6-trichlorophenol), cuprizone (CPZ; bicyclohexone oxaldihydrazone) and triethyl tin (TET; triethyl tin sulphate) in producing vacuoles in the brain of the Sprague-Dawley rat has been quantified by image analysis of the extent of the spongy change in the white matter.

4: Biochem J. 1971 Aug;124(1):221-34.
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Oxidative phosphorylation. The relation between the specific binding of trimethylytin and triethyltin to mitochondria and their effects on various mitochondrial functions.Aldridge WN, Street BW.1. A binding site (site 1) is present in mitochondria with affinity for trimethyltin and triethyltin adequate for a site to which they could be attached when the processes of energy conservation are inhibited. 2. The quantitative relationships between the binding of trimethyltin and triethyltin to site 1 and their effects on various mitochondrial functions have been examined. ............. Possible interpretations of these findings are discussed with reference to published arrangements for coupling of electron transport to ATP synthesis and also to our present knowledge of the chemical and biological specificity of trialkyltin compounds.


Cell Mol Neurobiol. 1994 Dec;14(6):591-7.

The public health significance of metal neurotoxicity.
Carpenter DO.
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509, USA.

Here is an excerpt from the article about the effect of the mitochondridrial neurotoxin,triethyltin, whose effects have been compared to hexachlorophene.

............. The organotins are the major concerns with regard to human health,
especially triethyltin, since the inorganic tins are not known to be toxic (Manzo et
al., 1985). Organotin compounds have a number of industrial uses as biocides,
catalysts, preservatives and polymer stabilizers. In the early 1950s, 110 people
died in France from taking a medicine which contained some triethyltin, and
patients showed nausea and vomiting, headache, photophobia, altered consciousness,
visual impairment, and convulsions (Foucin and Gruner, 1979). Those that
survived showed psychological and intellectual impairments. Triethyltin is an
uncoupler of oxidative phosphorylation which leads to cytotoxic brain edema and
pathological changes in myelin sheaths, axons, and astrocytes. Animal studies
have shown that triethyltin can produce behavioral and neurophysiological
changes at doses lower than those that produce brain edema (Fox and Doctor,
1983).......................