Acetaminophen-induced hepatotoxicity.

@article{James2003AcetaminopheninducedH,
  title={Acetaminophen-induced hepatotoxicity.},
  author={Laura P James and Philip R. Mayeux and Jack A. Hinson},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2003},
  volume={31 12},
  pages={
          1499-506
        }
}
The analgesic acetaminophen causes a potentially fatal, hepatic centrilobular necrosis when taken in overdose. The initial phases of toxicity were described in Dr. Gillette's laboratory in the 1970s. These findings indicated that acetaminophen was metabolically activated by cytochrome P450 enzymes to a reactive metabolite that depleted glutathione (GSH) and covalently bound to protein. It was shown that repletion of GSH prevented the toxicity. This finding led to the development of the… Expand
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The role of prostaglandin E2 in acute acetaminophen hepatotoxicity in mice.
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References

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TLDR
Nitric oxide is an important mediator of acetaminophen‐induced hepatotoxicity and is demonstrated to be correlated with expression of inducible nitric oxide synthase (iNOS) protein in these regions. Expand
Selective protein arylation and acetaminophen-induced hepatotoxicity.
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It is now apparent that the concept of a multistage process that involves both initiation and progression events is appropriate for APAP toxicity, and it is unlikely that a unique initiating event will ever be identified. Expand
Glutamate dehydrogenase covalently binds to a reactive metabolite of acetaminophen.
TLDR
The purified and identified a 50 kDa mitochondrial protein which becomes covalently bound to a reactive metabolite of acetaminophen and this data suggest thatacetaminophen hepatotoxicity may in part be mediated by covalent binding to glutamate dehydrogenase. Expand
Modulation of macrophage functioning abrogates the acute hepatotoxicity of acetaminophen
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Data indicate that the protection afforded the animals by pretreatment with macrophage modulators was not due to suppression of the formation of NAPQI and hence support the hypothesis that macrophages may contribute directly to acetaminophen hepatotoxicity by an independent mechanism. Expand
ROLE OF MACROPHAGES IN ACETAMINOPHEN (PARACETAMOL)‐INDUCED HEPATOTOXICITY
TLDR
Macrophages play an early and probably a direct role in mediating the liver damage due to acetaminophen, consistent with the role that macrophages have been shown to play in the pathogenesis of alcohol‐induced liver damage. Expand
Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation.
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A relationship between metabolic events in APAP toxicity and the upregulation of NO, and IL-1b is suggested and covalent binding per se does not appear to be a toxic event in the development of toxicity. Expand
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TLDR
The results demonstrate the ability of human CYP2E1 to activate APAP to reactive metabolites which form covalent protein adducts and cause toxicity to a hepatoma cell line. Expand
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TLDR
The data are consistent with NO having a critical role in controlling superoxide-mediated lipid peroxidation in acetaminophen hepatotoxicity and may be mediated by either lipidperoxidation or by peroxynitrite. Expand
Paracetamol (Acetaminophen)-Induced Toxicity: Molecular and Biochemical Mechanisms, Analogues and Protective Approaches
An overview is presented on the molecular aspects of toxicity due to paracetamol (acetaminophen) and structural analogues. The emphasis is on four main topics, that is, bioactivation, detoxication,Expand
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