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BMJ Open 13 , e071359 (2023)

Weight loss and all three pathways may contribute to this result

Baicalein and 12/15-lipoxygenase in the ischemic brain

Why do glutathione tablets take several weeks to show results

Their 1st paper confirmed APAP dosing was key & showed that liver injury was due to p450 metabolism4/ The 2nd Mitchell paper showed: 1Liver damage is directly proportion to covalent binding of an unknown toxic metabolite 2The binding happens in centrilobular liver 3Treatments that reduce the toxin's covalent binding lead to reduced liver injury5/ The 3rd Mitchell paper showed APAP liver damage is caused by a P450 metabolite, happening: 1When NADPH is available 2By oxidation It's prevented by glutathione/cysteine, showing that glutathiones role is to protect cellular proteins from attack by toxic metabolites6/ The 70% rule for glutathione: The 4th Mitchell paper showed liver damage, caused by covalent binding of the toxic metabolic to liver proteins, happens when 70% of the liver's glutathione is depleted (the 5th paper repeated experiments in a hamster model)7/ The full picture: Then Mitchell showed that most APAP is metabolized by glucoronidation, some by sulfation, and that liver injury happens when these pathways are overwhelmed by overdose and glutathione stores are 70% depleted leading to the p450 oxidative pathway8/ Based on these landmark studies, the authors summarized their work with this diagram - which we all learn today