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Wolters Kluwer Health, Philadelphia Gonzlez-Cruz AO, Hernndez-Jurez J, Ramrez-Cabrera MA, Balderas-Rentera I, Arredondo-Espinoza E (2022) Peptide-based drug-delivery systems: a new hope for improving cancer therapy

When intracellular GSH concentrations reached a low level, toxicity ensued.8 These early studies found a strong relationship between covalent binding of APAP to tissue proteins and cytotoxicity, leading to the proposal that these were causally linked.9 Early studies also demonstrated that freshly isolated hepatocytes were a good model for the metabolism and toxicity of APAP, including large species differences in sensitivity.10 It has now been very well established that the toxicity of APAP results from metabolic activation and there is also evidence that some of the analgesic properties of the drug may derive from in vivo biotransformation to an arachidonic acid conjugate of p -aminophenol ( N -arachidonoylphenolamine, or AM404) via fatty acid amide hydrolase.1113 The metabolism of APAP is illustrated in Fig

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