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Selective protein covalent binding and target organ toxicity.
Protein covalent binding by xenobiotic metabolites has long been associated with target organ toxicity but mechanistic involvement of such binding has not been widely demonstrated. ModernExpand
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Acetaminophen-induced inhibition of hepatic mitochondrial respiration in mice.
Morphological changes are observed in mitochondria early in the course of acetaminophen (APAP) hepatotoxicity. In order to determine if functional deficits also occur, this study examined the effectExpand
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A comparative study of mouse liver proteins arylated by reactive metabolites of acetaminophen and its nonhepatotoxic regioisomer, 3'-hydroxyacetanilide.
Acetaminophen (4'-hydroxyacetanilide), a widely used analgesic/antipyretic drug, is hepatotoxic in large doses, whereas the m-hydroxy isomer of acetaminophen, 3'-hydroxyacetanilide, is notExpand
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Origin and possible significance of alanine production by skeletal muscle.
Abstract These experiments were undertaken to determine the source of alanine released by skeletal muscle and to clarify the possible relationships between this process and the degradation ofExpand
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Selective protein arylation and acetaminophen-induced hepatotoxicity.
More than 20 years have passed since the early reports of acute hepatotoxicity with APAP overdose. During that period investigative research to discover the "mechanism" underlying the toxicity hasExpand
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Compartmentation of free amino acids for protein synthesis in rat liver.
The concept that a general intracellular pool serves as the sole precursor of amino acids for protein biosynthesis has been vigorously debated in recent years. To help resolve this controversy, weExpand
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Differential detergent fractionation of isolated hepatocytes: Biochemical, immunochemical and two‐dimensional gel electrophoresis characterization of cytoskeletal and noncytoskeletal compartments
Two‐dimensional (2‐D) gel electrophoresis is often used in toxicologic and metabolic studies to assess treatment‐ or stage‐specific changes in protein synthesis, degradation or posttranslationalExpand
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Acetaminophen nephrotoxicity in CD-1 mice. I. Evidence of a role for in situ activation in selective covalent binding and toxicity.
Acetaminophen (APAP) administration (600 mg/kg, ip) to 18-hr-fasted, 3-month-old male CD-1 mice results in necrosis of the renal convoluted proximal tubules. To selectively inhibit APAP activation inExpand
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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.
Acetaminophen (APAP) is a widely used analgesic and antipyretic that can lead to severe liver damage when taken at excessive doses. APAP toxicity results when cytochrome P450-generated APAPExpand
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Immunohistochemical localization of acetaminophen in target tissues of the CD-1 mouse: correspondence of covalent binding with toxicity.
Administration of hepatotoxic doses of acetaminophen (APAP) to mice results in necrosis, not only of liver cells but of renal proximal tubules and bronchiolar and olfactory epithelium. In the liver,Expand
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