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Selective protein covalent binding and target organ toxicity.
TLDR
Metabolites of acetaminophen, halothane, and 2,5-hexanedione form covalently bound adducts to recently identified protein targets, and selective binding to specific cellular target proteins may better correlate with toxicity than total protein covalent binding.
A comparative study of mouse liver proteins arylated by reactive metabolites of acetaminophen and its nonhepatotoxic regioisomer, 3'-hydroxyacetanilide.
TLDR
3'-hydroxyacetanilide should prove to be a useful tool to aid in the discrimination of hepatic acetaminophen protein adducts that may be critical or noncritical to survival of hepatocytes.
Origin and possible significance of alanine production by skeletal muscle.
TLDR
Alanine production does not reflect protein degradation in muscle but instead appears to be synthesized de novo primarily from exogenous glucose and from amino groups released by catabolism of branched chain amino acids, suggesting the existence of a brancED chain amino acid-alanine cycle in the organism.
Selective protein arylation and acetaminophen-induced hepatotoxicity.
TLDR
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.
Compartmentation of free amino acids for protein synthesis in rat liver.
TLDR
The distribution of intraperitoneally administered [(3)H]valine in the tRNA and the extracellular and intracellular compartments of rat liver is followed and it is unlikely that the valyl-tRNA is charged exclusively with amino acids derived from the extacellular pool.
Differential detergent fractionation of isolated hepatocytes: Biochemical, immunochemical and two‐dimensional gel electrophoresis characterization of cytoskeletal and noncytoskeletal compartments
TLDR
A differential detergent fractionation (DDF) protocol is defined and characterized to enable protein dynamics in cytoskeletal and noncytOSkeletal compartments of isolated hepatocytes to be monitored simultaneously and reproducibly partitions hepatocytic proteins into functionally different compartments that are readily analyzed by 2‐D gel electrophoresis.
Acetaminophen nephrotoxicity in CD-1 mice. I. Evidence of a role for in situ activation in selective covalent binding and toxicity.
TLDR
It is suggested that, for the mouse, intrarenal biotransformation of APAP to a reactive electrophile significantly contributes to the APAP covalent binding within the kidneys and the subsequent nephrotoxicity.
Modulation of serum growth factor signal transduction in Hepa 1-6 cells by acetaminophen: an inhibition of c-myc expression, NF-kappaB activation, and Raf-1 kinase activity.
TLDR
It is shown that APAP also inhibits entrance of Hepa 1-6 cells into the cell cycle by blocking a number of events associated with the G0-G1 transition and inhibits serum growth factor activation of c-myc expression, NF-kappaB DNA binding, and Raf kinase.
Immunohistochemical localization of acetaminophen in target tissues of the CD-1 mouse: correspondence of covalent binding with toxicity.
TLDR
It is demonstrated that covalent binding and subsequent necrosis are localized in common with cytochrome P4502E1, suggesting that, as in the liver, toxicity in extrahepatic targets is also related to the ability of these tissues to activate APAP in situ.
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