Medline Article Cita

Medline Article Citations

There are hundreds of articles about hexachlorophene cited in Pub Med.Since hexachlorophene (commonly known by one of its brand names, PhiSoHex) is effectively used to combat the bacteria staphylococcus, many of the citations concern this use.
However you can also see many of the hexachlorophene citations in the area of its toxicology. Particularly in the 60s and 70s, both human and animal research began to show the toxicological mechanisms of hexachlorophene. It should be noted that the accumulation of this research and the abnormalities of the autopsies of babies resulted in the severe restrictions on the use of hexachlorophene. Below are just a few of the numbers of relevant hexachlorophene citations.

National Library of Medicine Gateway listings:
In their search of Medline/Pub Med journal citations and abstracts they found 1207.
In their search of TOXLINE for toxicology citations they found 276.
In their search of DART for developmental and reproductive toxicology articles they found 65 citations.

Within Medline/PubMed one must be careful to note that the mere search for a word like hexachlorophene will turn up citations of articles where hexachlorophene is only a side issue. The same is especially true when hexachlorophene is one of two search words. Even so, it might be helpful to start an investigation of hexachlorophene’s toxicological effects by noting this: hexachlorophene with liver occurs in 70 articles; hexachlorophene with brain occurs in 113 articles; hexachlorophene and myelin occurs in 41 articles. I've noted in prior posts that some of the articles in each of these areas do indicate hexachlorophene toxicological effects in both animal and human studies.

neurochemical effect

This is another citation of hexachlorophene and other myelin toxins in a neurochemistry text.

Many chemical toxins can impair myelin formation or cause its breakdown
These include lead, cuprizone, lysolecithin, organotin, hexachlorophene and tellurium. Lead is a common environmental pollutant that causes hypomyelination and demyelination [1]. Cuprizone and lysolecithin are toxins that frequently have been used experimentally in the context of investigating remyelination [1, (image placeholder)5] (see below). Systemically administered cuprizone has a direct toxic effect on oligodendrocytes, whereas lysolecithin causes lysis of myelin sheaths themselves when administered focally. Triethyltin and hexachlorophene cause an edematous demyelination with splitting at the intraperiod line but without apparent damage to myelin-forming cells [1]. Tellurium treatment of young rats causes a highly synchronous demyelination and remyelination in sciatic nerve that is associated with the inhibition of cholesterol synthesis by some metabolite of this element [ (image placeholder)26]. A detailed description of the effects of these and other chemical toxins on the biochemistry of myelin is beyond the scope of this chapter, but they have been covered in more detail in earlier editions of this book or in other sources [1].
General undernourishment or dietary deficiencies of specific substances can lead to a preferential reduction in myelin formation
Much of the CNS myelin in mammals is formed during a relatively restricted time period of development, corresponding to the final prenatal months and the first few years of postnatal life in humans and 15 to 30 days of postnatal life in rats. Just before this rapid deposition of myelin, there is a burst of oligodendroglial proliferation. During these restricted periods of time, large portions of the metabolic activity and synthetic capacity of the brain are involved in myelinogenesis. Any metabolic insult during this "vulnerable" period may lead to a preferential reduction in myelin formation [1]. The most vulnerable period appears to be the time of oligodendroglia proliferation since animals deprived of food in this period have an irreversible deficit of myelin-forming cells and hypomyelination.

Hexachlorophene Toxi

Hexachlorophene Toxicity to French Babies

This is part of a Center For Disease Control report that briefly notes to French epidemiological study of the autopsies of the French babies who died after receiving hexachlorophene.



h. Hexachlorophene can be lethal from percutaneous absorption.  Children may be specifically susceptible. 
i. Hexachlorophene (6.3%) was added to “baby powder” in France due to a manufacturing error.  It caused encephalopathy and ulcerative skin lesions.  36 of 204 exposed children died within a few days of exposure (Martin-Bouyer et al., 1982). 
ii. pHisoHex® soap contains 3% hexachlorophene.  Repeated bathing of premature children in undiluted pHisoHex has been associated with a vacuolar encephalopathy and lower survival rates.  A study of 248 children autopsied over a 7.5 year period showed encephalopathy in 17 infants (Shuman et al., 1974).  PHisoHex has been restricted to prescription use or as a surgical scrub for health care personnel since 1972 (Freeman and Maibach, 1991).

At that time it was not possible to do brain imaging studies on the babies who lived.  Now of course it is possible.  It's certainly reasonable to expect that a pattern of abnormalities in the myelin may appear.  Based on hundreds of studies listed in Pub Med one might expect that two of the most likely structural areas of the brain may be the cerebellum and the brainstem.  

Mitochondria

Mitochondria
And
Neurological Disorders
And
The Human Mitochondrial Neurotoxin, Hexachlorophene



The purpose of this paper is to raise some questions. They are based on a review of the biomedical research on mitochondria, neurological disorders, and the human neurotoxin, hexachlorophene. The questions, based upon the review, are raised in the hope that those with more specific expertise will see the value of exploring the quite real possibility that brain imaging of those who were exposed to hexachlorophene may show a specific pattern of neurological abnormalities. Will these brain imaging results of adults who were exposed to hexachlorophene as babies correlate with the specific pattern of neurological abnormalities shown in autopsies of the babies who died after being exposed to hexachlorophene?


Some questions raised are these: Today, who has those hexachlorophene-related mitochondrial abnormalities? We know babies and children are more vulnerable because the skin is more permeable, but what are the other exposure vulnerabilities. Are they, for some, also caused by an interaction with their specific genetics? Could brain imaging show abnormalities in the myelin of the cerebellum and other areas of the brain that are characteristic of this particular mitochondrial neurotoxin? Is there sufficient evidence to go ahead and assess a possible causal relationship between specific behavioral symptoms related to structural and functional brain abnormalities? Could brain imaging show a relationship between therapeutic variables, behavioral symptoms, and changes in structural and functional brain abnormalities?

Other mitochondrial neurotoxins (for example, triethyltins, cuprizone, MPTP,3-NP) have been used as causal variables in model neurological disorders (for example, Huntington's, ALS, Parkinson's, etc.). Each of these neurotoxins have different neurological effects. For example, a recent study(Klivenyi,P 2005) contrasted the effects of the toxin model for Parkinson's(MPTP) and the toxin model for Huntington's(3-NP). Both mitochondrial neurotoxins caused changes in amino acids. But they caused two different amino acid neurotransmitter effects. It would seem quite reasonable that a similar research approach would show that hexachlorophene would result in a third specific amino acid neurotransmitter effect. We know it has its own neurological disorder pattern.

From the past epidemiological study of the autopsies of the babies, we already know that it is a specific human mitochondrial neurotoxin. Hexachlorophene's effects, now, can be studied in adults by means of brain imaging. It's an opportunity that wasn't there before; it's an opportunity we should take advantage of now.

MITOCHONDRIAL NEUROT

MITOCHONDRIAL NEUROTOXINS AND OLIGODENDROCYTES/ MYELIN: THE HUMAN NEUROTOXIC PROCESS OF HEXACHLOROPHENE


Hexachlorophene is a mitochondrial neurotoxin that is especially toxic to developing oligodendrocytes. Myelin with water-filled spaces or vacuoles is a biomarker for hexachlorophene effects.

One of the ways in which hexachlorophene differs from other mitochondrial neurotoxins is the locations in the brain where it affects white and gray matter. Hexachlorophene is toxic to the cerebellum, the hippocampus and the brainstem among other areas of the brain.  One of the most consistent findings in both human and animal research with hexachlorophene is its toxicity to the cerebellum.

Research with humans in the late 60s and early 70s showed hexachlorophene’s neurotoxicity to babies.An epidemiological study in France found that babies who received talcum powder with hexachlorophene in excessive amounts, died.  Upon autopsy, they showed characteristic hexachlorophene abnormalities in their myelin.  About the same time, in America, research with babies and young children were showing examples of hexachlorophene related neurotoxicity.  As a result of this hexachlorophene use was severely restricted, essentially limited to adults.

One of those who participated in this research explained how difficult it was to do such research on such a widely used medical product.  It would seem that the difficulty must have continued.  One would expect more follow-up research on the possible long-term effects of hexachlorophene on those who received it at the vulnerable periods of their lives.

Two things have happened since that time.  One is that those who received hexachlorophene early in their lives are now in their 30s, 40s, 50s, and 60s.  Long-term effects on those who were most vulnerable are now possible.  The second thing has to do with brain imaging advancements.  The assessment of the long-term effects of hexachlorophene on both gray and white matter in the brain seems possible.

Effects of Mitochond

Effects of Mitochondrial Toxins Including Hexachlorophene : The Process of Liver Damage

Other papers have reviewed the effects of hexachlorophene as a mitochondrial neurotoxin. This paper will review an additional effect of hexachlorophene and other toxins of its preventing the mitochondrial production of ATP.
Adenosine Triphosphate (ATP) is vital because it is used to store energy in the cell's mitochondria. During oxidative stress this stored energy is used to defend the cell fom damage or death.

The specific result of these mitochondrial toxins on the liver is damage or death to the liver cells. In addition to hexachlorophene there are a number of herbicides and pesticides that affect the mitochondria of liver cells and, in turn, affect the viability of these cells. One of these herbicides is called dinoseb. Liver cell death by dinoseb starts in the mitochondria because it also leads to the depletion of ATP.

Another mitochondrial toxin to the liver is called Tacrine. It has been used in the treatment of Alzheimer's disease. However tacrine has been shown to accumulate within the mitochondria, and has targeted the mitochondrial DNA. Again, its effect of uncoupling oxidative phosphorylation is ATP depletion.

So,hexachlorophene, in addition to its neurological effects, is also toxic to liver cells. Again, hexachlorophene is a mitochondrial liver toxin as well as a neurotoxin. In both the brain and the liver it uncouples oxidative phosphorylation and interferes with the production of ATP. There is this same biochemical mechanism with similar effects. This depletion can result in either cellular damage or death. Repeated use of hexachlorophene repeats these toxic cellular effects.

This will be a blog about research dealing with the antibacterial, hexachlorophene. It will focus on hexachlorophene as a mitochondrial neurotoxin. It will cite both animal and human research that showed the toxic effects of hexachlorophene on the central nervous system myelin. It will focus on hexachlorophene's toxic effects on brain locations including the cerebellum, the hippocampus, and the brainstem.

Studies cited will include the epidemiological studies of the autopsies of babies in France who died after exposure to hexachlorophene and then showed its toxic effects in their myelin. There will also be citations of developmental effects of babies exposed to hexachlorophene. In addition to hundreds of studies about the mitochondrial neurotoxin, hexachlorophene, there have been an increasing number of recent studies of the effects of other mitochondrial neurotoxins on the central nervous system. Their effects, in many ways, reflect the common mitochondrial neurotoxic mechanism that they share with hexachlorophene.

It's especially interesting that these comparable mitochondrial neurotoxins and their effects are used as animal and human models of neurological and psychiatric disorders. These mitochondrial neurotoxins are used as models for Parkinson's, Huntington's, ALS, and other neurological disorders that affect different locations in the brain.

One of the most encouraging advancements in research is brain imaging of the effects of mitochondrial neurotoxins such as those that have become models of neurological and neuropsychiatric disorders.

In the early 1970s,when hexachlorophene was discovered to be a human mitochondrial neurotoxin, it only happened because autopsies were done after the deaths of those babies exposed to 6% hexachlorophene talcum powder. But now it is possible for hexachlorophene research to be updated. That is because its effects on those who lived can be investigated in the same way as other comparable neurotoxins have recently been reinvestigated.

Recent research on its fellow mitochondrial neurotoxins has resulted in much more information because brain imaging allows a much more sensitive exploration of the continuing toxic effects of these mitochondrial neurotoxins on the living brain. The question now is how much more we will find out when we use brain imaging to investigate what we already know is a comparatively toxic compound -- hexachlorophene.