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Potent Activation of Indoleamine 2,3-Dioxygenase by Polysulfides, 2019, Groves et al

Discussion in 'Other health news and research' started by Andy, Aug 23, 2019.

  1. Andy

    Andy Committee Member

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    Paywall, https://pubs.acs.org/doi/10.1021/jacs.9b07338
    Sci hub, https://sci-hub.se/10.1021/jacs.9b07338
     
    Andy, Aug 23, 2019
    #1
    junkcrap50, Samuel, Hutan and 7 others like this.
  2. alex3619

    alex3619 Senior Member (Voting Rights)

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    Something that activates IDO1 may be trialed at some point, at least in vitro. The problem with IDO2 only arises when the kinetics of IDO1 become poor. The issue here though is that the kinetics must be enhanced at high concentrations of tryptophan, and I doubt any of the drugs have been tested under those conditions.
     
    alex3619, Aug 23, 2019
    #2
    FMMM1, Kitty, Lisa108 and 2 others like this.
  3. Hutan

    Hutan Moderator Staff Member

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    I'm trying to get my head around this. So, the paper is saying that polysulfides activate IDO1, and activated IDO1 suppresses the immune response, mediating inflammation and auto-immune reactions. And the thinking around the trap idea is that IDO1 isn't working well? So maybe polysulfides might help ME?

    For what it's worth:
    The onset of illness for my children and I coincided with a gastrointestinal upset (well, a fairly severe one with my daughter in hospital for 3 nights due to the pain - all three of us were affected), but also a heat wave and the arrival of a container load of our personal effects from a country with very lax controls on fumigation. The goods had been treated with methyl bromide, which had reacted with some of the materials (wool, feather pillows, natural rubber mattresses, leather sofas) to create horrendously smelling polysulphides.

    We were shut up in the house because the 40 degree C plus temperatures outside meant opening windows or going outside was a bad idea, and we were opening up boxes in the heat.

    I don't know if the skin contact and the inhalation would have affected levels of these compounds in our bodies. But, if they did, then potentially we had high levels of polysulphides, which, if I'm reading this paper right, should have activated IDO1. Which is the opposite of what the trap theory proposes?

    Although, this possible perturbation of the IDO1 function was at a time when we were dealing with an infection, and so perhaps immune systems were activated. And then there was the heat and the lack of sleep due to heat. And so maybe all of that messed homeostasis up, kicking things so far into overdrive that there was a swing back in the other direction?

    Thinking today is like walking through treacle, and I'm not sure that I'd do better with this on a good day. The exposure of my children and I to polysulphides around the time of illness onset seemed something worth mentioning. Maybe others can make some sense of it?

    There are so many unknowns. Poking a stick at things might bring change, but maybe not good change.
     
    Last edited: Aug 24, 2019
    Hutan, Aug 24, 2019
    #3
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  4. pteropus

    pteropus Senior Member (Voting Rights)

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    FWIW, i've recently been prescribed pentosan polysulphate sodium (PPS).
    is there a possibility that it might increase my IDO1 function ?
     
    pteropus, Aug 25, 2019
    #4
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  5. Amw66

    Amw66 Senior Member (Voting Rights)

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    Indole as signalling from C difficile - interesting as gut testing via stool analysis has just highlighted c diff as being high for my daughter, but only symptom is tightness. Also gut microbioa which suggest seratonin/p[hase 2 lover detox issues. becoming very interesting.


    "Clostridium difficile Modulates the Gut Microbiota by Inducing the Production of Indole, an Interkingdom Signaling and Antimicrobial Molecule" Charles Darkoh,a,b Kimberly Plants-Paris,a Dayna Bishoff,a Herbert L. DuPonta,b

    https://msystems.asm.org/content/msys/4/2/e00346-18.full.pdf

    tagging @Perrier
    eta added tag
     
    Last edited: Sep 3, 2019
    Amw66, Sep 3, 2019
    #5
  6. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Basically Kynurenine surpresses the immune system; so low Kynurinine may mean more risk of autoimmunity. IDO1/2 convert trypotophan to Kynurinine. Yes the trap suggests that lowering intracellular tryptophan (using IDO1/2) means that you should return to normal. This suggests that polysulfides may increase the activity of IDO1 - which is what you are looking for. Check out @alex3619 comments though.

    I used to be sceptical of chemical sensitivities - I'm much less so now. Good luck.
     
    FMMM1, Oct 24, 2019
    #6
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