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Acetaminophen-protein adducts

Muldrew, K. L., James, L. P., Coop, L., McCullough, S. S., Hendrickson, H. P., Hinson, J. A., and Mayeux, P. R. (2002). Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection. Drug Metab. Dispos. 30 446-451. [Pg.292]

Fig. 1 Immunohistochemical time course for acetaminophen protein adduct fonnatirai and hepatic necrosis in mice treated with a toxic dose of acetaminophen. The liver sections were immuno-chemically stained using antiacetaminophen-cysteine antiserum. The hepatocytes containing the adducts are stained red. Note the appearance of valcuoles and pycnotic nuclei indicative of necrosis only in the hepatocytes containing acetaminophen-protein adducts at 2 and 6 h. Staining was not observed in livers of saline treated mice (data not shown) (Roberts et al. 1991)... Fig. 1 Immunohistochemical time course for acetaminophen protein adduct fonnatirai and hepatic necrosis in mice treated with a toxic dose of acetaminophen. The liver sections were immuno-chemically stained using antiacetaminophen-cysteine antiserum. The hepatocytes containing the adducts are stained red. Note the appearance of valcuoles and pycnotic nuclei indicative of necrosis only in the hepatocytes containing acetaminophen-protein adducts at 2 and 6 h. Staining was not observed in livers of saline treated mice (data not shown) (Roberts et al. 1991)...
Clinical data also support the association of covalent binding and toxicity. Early studies utilized immunoassays to detect adducts in the blood samples of patients with acetaminophen overdose (Hinson et al. 1990). The highest levels of adducts were found in the patients with the most severe toxicity. The recent development of a highly sensitive and specific HPLC-EC assay for detection of acetaminophen protein adducts (3-cysteine-acetaminophen in proteins) has allowed for further... [Pg.374]

Fig. 2 hnmunohistochemical comparison of cellular locahzation of acetaminophen-protein adducts to nitrotyrosine in hepatic proteins of mice treated with a toxic dose of acetaminophen. Mice were treated with acetaminophen (300 mg kg ) or saline and livers removed at 4 h. [Pg.379]

Dahlin DC, Miwa GT, Lu AY, Nelson SD (1984) N-acetyl-p-benzoquinone imine a cytochrome P-450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci USA 81 1327-1331 Davem TJ 2nd, James LP, Hinson JA, Poison J, Larson AM, Fontana RJ, Lalani E, Munoz S, Shakil AO, Lee WM (2006) Measurement of serum acetaminophen-protein adducts in patients with acute liver failure. Gastroenterology 130 687-694 Davidson DG, Eastham WN (1966) Acute liver necrosis following overdose of paracetamol. Br Med J 5512 497 99... [Pg.397]

Janies LP, Lamps LW, McCullough S, Hinson JA (2003a) Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse. Biochem Biophys Res Commun 309 857-863 James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davem TJ, Lee WM (2009) Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen ovtadose and acute liver failure. Drag Metab Dispos 37 1779-1784. Published online May 13, 2009 10.1124/dmd.l08.026195... [Pg.400]

Roberts DW, Pumford NR, Potter DW, Benson RW, Hinson JA (1987) A sensitive immunochemical assay fra acetaminophen-protein adducts. J Pharmacol Exp Ther 241 527-533... [Pg.403]

Roberts DW, Bucci TJ, Benson RW, Warbritton AR, McRae TA, Pumford NR, Hinson JA (1991) Immunohistochemical localization and quantification of the 3-(cystein-S-yl)-acetaminophen protein adduct in acetaminophen hepatotoxicity. Am J Pathol 138 359-371 Rose PG (1969) Paracetamol overdose and liver damage. Br Med J 1 381-382 Rumack BH, Peterson RG (1978) Acetaminophen overdose incidence, diagnosis, and management in 416 patients. Pediatrics 62 898-903... [Pg.404]

LP James, Capparelli EV, Hinson JA, Dalvem TJ, Lee WM (2007) Pharmacokinetic analysis of acetaminophen protein adducts in adults with acute liver failure. Clin Pharmacol Ther 81 2 Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH (1988) Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 319 1557-1562... [Pg.404]

We perceived the need for sensitive assays that do not rely on the use of radioisotopes or extensive analytical methodology and that could accurately detect protein-bound acetaminophen in biological fluids in the presence of unbound acetaminophen. To this end, we recently developed sensitive avidin biotin-amplified ELISA (A-B ELISA) and particle concentration fluorescence immunoassays (PCFIA) which use antiserum specific for the major acetaminophen-protein adduct associated with toxicity (13-16). These assays are new tools to study the relation between formation of the 3-Cys-A protein adduct and acetaminophen-induced toxicity. In this report we review how these assays were developed, validated in laboratory animals, and used to quantify 3-Cys-A protein adduct formation in human acetaminophen overdose patients. [Pg.315]

This antiserum has also been used to detect acetaminophen-protein adducts in Western blots of serum and liver fractions from acetaminophen-dosed animals (1 ) and to localize the 3-Cys-A adduct in target tissues (17 and Bucci et al. this volume). [Pg.319]

Figure 5. Effect of substitution level on quantitation in the competitive A-B ELISA. The substitution levels based on the nmoles of [3H] NAPQI per mg of protein were ( ) 30, ( ) 10, ( ) 5, ( ) 3, ( ) 1, ( ) 0.5. In panel A acetaminophen-protein adducts were expressed in terms of protein concentration and in panel B, the same inhibition data was plotted as a function of covalently bound acetaminophen equivalents based on radioactivity (Reproduced from Ref. 19). Figure 5. Effect of substitution level on quantitation in the competitive A-B ELISA. The substitution levels based on the nmoles of [3H] NAPQI per mg of protein were ( ) 30, ( ) 10, ( ) 5, ( ) 3, ( ) 1, ( ) 0.5. In panel A acetaminophen-protein adducts were expressed in terms of protein concentration and in panel B, the same inhibition data was plotted as a function of covalently bound acetaminophen equivalents based on radioactivity (Reproduced from Ref. 19).
Table II. Concordance between Hepatotoxicity and Acetaminophen-Protein Adducts... Table II. Concordance between Hepatotoxicity and Acetaminophen-Protein Adducts...
Immunohistochemical Detection of Antigenic Biomarkers in Microwave-Fixed Target Tissues Acetaminophen—Protein Adducts... [Pg.327]

Previous reports described an ELISA specific for 3-Cys-A protein adducts that does not rely on radiolabeled samples (1 ) characterization of the relevant epitope (H) and quantification of 3-Cys-A adducts in liver and serum as a function of hepatotoxicity (9). This higlily characterized antiserum specific for the acetaminophen-protein adduct, 3-Cys-A, was used to correlate the immunohistochemical localization of 3-Cys-A protein adducts with the development of cell injury, in microwave-fixed liver. [Pg.329]

See other pages where Acetaminophen-protein adducts is mentioned: [Pg.124]    [Pg.373]    [Pg.373]    [Pg.378]    [Pg.379]    [Pg.393]    [Pg.324]    [Pg.330]    [Pg.358]    [Pg.627]   
See also in sourсe #XX -- [ Pg.373 ]



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