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Aspirin protects the liver from paracetamol

Discussion in 'Scientific Studies' started by haidut, Apr 17, 2015.

  1. haidut

    haidut Member

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    As many of you know paracetamol is very toxic to the liver and the mechanism of action is rapid depletion of glutathione (GSH). This study shows that aspirin protected the liver from GSH depletion induced by paracetamol. So, the next time your doctor tells you that aspirin is bad for the liver show him/her this study:):

    http://www.ncbi.nlm.nih.gov/pubmed/2569524

    "...Simultaneous administration of an equimolar dose of ASA resulted in a reduction of the paracetamol-induced depletion of GSH in all instances except for those rats that were not pretreated and those given 3-MC. Benorylate, the ASA ester of paracetamol, depressed rat liver GSH to levels comparable to those produced by the combination of paracetamol and ASA. ASA itself caused only minor changes in liver GSH concentrations. The results demonstrate that ASA causes a diminution of paracetamol-induced GSH depletion in rats with phenobarbitone type of enzyme induction. Inhibition of the formation of the reactive metabolite of paracetamol or reduction of the absorption rate of paracetamol seem to be unlikely as mechanisms underlying the ASA-induced effect. An ASA-mediated effect via changes of the hepatic thiol status is proposed."
     
  2. BingDing

    BingDing Member

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    Bump, great info, at least at my level of understanding. Thanks, haidut!
     
  3. Stuart

    Stuart Member

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    @ Haidut.
    Just curious what the recommended daily dose of aspirin is?
     
  4. OP
    haidut

    haidut Member

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    Depends on the condition/context. There is no recommended dose really. At doses of 20mg/kg - 30mg/kg daily aspirin optimally uncouples mitochondria. More or less than that reduce the effect.
    If higher metabolism is the ultimate/chronic goal then that dose would seem to be optimal. But, again, everything depends on context.
     
  5. Makrosky

    Makrosky Member

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    What do you mean by "less than that reduce the effect"?

    If you take less than 20mg/kg of aspirin is counter productive?
     
  6. OP
    haidut

    haidut Member

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    I mean less than 20mg/kg will uncouple mitochondria less. Same with more than 30mg/kg. Below certain dose (probably 10mg/kg) it won't uncouple at all but will have other benefits such as lower inflammation and thinner blood.
    Here is a thread with some more info:
    viewtopic.php?f=75&t=6130

    As you can see the uncoupling effect has an inverted U-shape with 0.5mM being optimal. In humans doses of 20mg/kg - 30mg/kg achieve about 0.5mM concentrations.
     
  7. Makrosky

    Makrosky Member

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    All right thanks for the clarification man!
     
  8. What-a-Riot

    What-a-Riot Member

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    "...Simultaneous administration of an equimolar dose of ASA resulted in a reduction of the paracetamol-induced depletion of GSH in all instances except for those rats that were not pretreated and those given 3-MC"

    So does aspirin limit glutathione by inhibiting liver enzymes? I've certainly heard of it inhibiting or competing for glucuronidation and sulfation, don't recall anything about glutathione conjugation offhand. Anyone know the significance of it failing to reduce GSH depletion by acetaminophen under normal conditions?
     
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