The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Organophosphate Dichlorvos and mitochondria toxicity

Discussion in 'General ME/CFS Discussion' started by pattismith, Oct 2, 2017.

  1. pattismith

    pattismith Senior Member

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    @Hip, @MeSci


    Toxicology. 2010 Apr
    Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos.

    Abstract
    Although the effects of acute pesticide poisoning are well known but, hardly any data exists regarding the health effects after long-term low-level exposure. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The present study elucidates a possible mechanism by which chronic organophosphate exposure (dichlorvos 6 mg/kg b.wt., s.c. for 12 weeks) causes liver dysfunction. Mitochondria, a primary site of cellular energy generation and oxygen consumption represent a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic dichlorvos exposure on liver mitochondrial electron transport chain (ETC), mitochondrial calcium uptake and its implications on the induction of liver enzymes and liver dysfunction in rodent model. Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I and II activity. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria isolated from dichlorvos (DDVP) treated rat liver. Mitochondrial preparation from DDVP treated rat liver demonstrated significant increase in mitochondrial Ca(2+) uptake and increase ROS levels. The alterations in the mitochondrial calcium uptake, mitochondrial electron transfer enzyme activities and increase ROS levels in turn might have caused an increase in liver enzymes (ALT, AST and ALP). The electron micrographs of liver cells depicted morphological changes in mitochondria as well as nucleus following 12 weeks of exposure to DDVP. These studies provide an evidence of impaired mitochondrial bioenergetics which may lead to liver dysfunction after chronic exposure to dichlorvos.
     
  2. Valentijn

    Valentijn Senior Member

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    Today is 25th anniversary of a cargo plane crash in the Netherlands which hit two large apartment buildings on the outskirts of Amsterdam. 190 liters of Dimethyl methylphosphonate (an organophosphate) was part of the cargo, though that was not made public until 6 years after the incident.

    From Wikipedia:
     
    Last edited: Oct 4, 2017
  3. Hip

    Hip Senior Member

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    Studies in Scotland showed that farmers using organophosphate-based sheep dip have a 4 times higher prevalence of ME/CFS than the national average. Ref: 1

    ME/CFS researcher Prof Peter Behan decades ago tried to bring to attention the link between organophosphates and ME/CFS, but was apparently thwarted and ridiculed by a pesticide industry.

    This is what @Abha told me in a PM:
    OP = organophosphate
     
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  4. brenda

    brenda Senior Member

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    I was part of the sheep dip farmers class action though mine was a house spraying by a local authority to eradicate an infestation on a new tenancy but what happened was that legal aid was withdrawn so that no-one could afford to sue.
     
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  5. Countrygirl

    Countrygirl Senior Member

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    We have been here before. This is a post I wrote here on Dec 16th 2009:

     
  6. Countrygirl

    Countrygirl Senior Member

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    And there is this:


    https://www.theguardian.com/science/2017/aug/19/sick-crew-toxic-air-planes-frequent-flyers-ill

    This is part of the article from the Guardian:



     
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  7. pattismith

    pattismith Senior Member

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    I was myself exposed to Dichlorvos/Fenitrothion on a recurrent basis from a Dog spray insecticide (it was prohibited soon after), so I believe the more we talk about organoP toxicity, the better it is.:thumbsup:
     
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  8. bertiedog

    bertiedog Senior Member

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    From:http://cdn.intechopen.com/pdfs/2567...cytochrome_p450_enzymes_in_vitro_a_survey.pdf

    Presumably if you have various SNPs in some of these enzyme systems then it could make the problem worse of getting rid of these chemicals by our own detoxification system.

    I know I have some of these SNPs specifically related to detoxification of organophosphates and in the 80s I remember that when I would put a flea spray on my Retriever which contained this chemical I would feel horrific and nearly fall over with dizziness. It was pretty immediate and not dissimilar to the effect I get if I eat any MSG which of course is a different process (breaking down an amine where again I have problems).


    "Cytochrome P450 enzymes (CYPs) are active in the metabolism of wide variety of xenobiotics. The investigation of the contributions of human CYPs in pesticides metabolism, especially insecticides, is still growing. One of the background tools to facilitate this task is by sorting the contribution of each human CYP isoform in the metabolism of pesticides. This paper attempts to provide a comprehensive literature survey on the role of human hepatic CYPs such as human CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5 and CYP3A7 in pesticides biotransformation in vitro as well as to sort the reactions mediated. Based on relevant publications identified by searching databases from 1995 through 2011, more than 400 metabolic reactions were reported to be mediated at least in part by human CYPs in vitro. Some information on older papers was obtained from previous literature surveys compiled by Hodgson 2001 & 2003. Finally, we give brief insight into potential modulations and consequences of human CYP genes – pesticides interactions. "

    Pam
     
  9. pattismith

    pattismith Senior Member

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    Thank you Valentijn, I didn't know this horrific accident;

    It is unclear in the wikipedia page if the health issues of the survivors were a result of the deplete uranium contamination or the organophosphate...

    Interestingly, deplete uranium weapons were heavily used in Gulf war...

    https://southfront.org/depleted-uranium-radioactive-contamination-iraq-overview/

    an extract:


    • "Pathological Studies of DU Effects on Human Health
    Dr. Huda Ammash- Professor of Molecular Biology in the College of Science in University of Baghdad, 1998, presented a paper on the mechanisms of toxicity induced by free radicals resulting from irradiation with DU and ionization of the atmosphere in Iraq [42] [43]. This paper pinpointed the need for DU toxicity studies on enzymes (SOD), Caralase, hydrogenates and Glyceraldehydes Dehydrogenates levels. She also presented the multi aborative cases on the DNA level where out of 50 studied cases, 29 cases were found with DNA abnormalities (with no hereditary evidence). Other multi aborative cases investigating the toxoplasmosis effect showed that out of 130 cases, over 65% more were infected than those recorded in 1989.

    Muhammed, Z.T. et al, 2002, [44] published a paper about the effects of DU radiation on the human immune system enzyme. A group of (26) Iraqi veterans who were exposed to DU radiation with (43) control individuals were all subjected to tests for Adenosine DA Amines (ADN) enzyme activity. Results indicated mean activity of the enzyme of the exposed individuals of (0.184 ±0.016) U/gm protein, while the unexposed individual’s enzyme activity (0.291 ±0.022) U/gm protein.

    ADA enzyme activity in the exposed individuals were found to be significantly lower than the control group. P<0.05 significant correlation coefficient was found between ADA activity as an important immune enzyme and related clinical signs and symptoms related to defective cellular immune functions.

    Ammash, H., Alwan, L. and Marouf, B.A.,2002, published a paper (in Arabic) [45] about the results of Genetic hematological analysis for a group of individuals who live in DU contaminated areas in Southern Iraq. Blood tests for the (47) individuals who lived in Basra contaminated areas and other (30) individuals as a control group who lived in Baghdad. The research included other clinical and correlated factors."
     
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  10. mariovitali

    mariovitali Senior Member

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    CC @Jesse2233


    https://www.ncbi.nlm.nih.gov/pubmed/25869557
     
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