ACETAMINOPHEN ADDUCTS AND METHODS OF USE THEREOF
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Abstract
The present disclosure relates to acetaminophen protein adducts and methods of diagnosing acetaminophen toxicity using the acetaminophen protein adducts. The present disclosure provides acetaminophen (APAP)-protein adducts and methods of detecting acetaminophen-induced toxicity in a subject using APAP-protein adducts. One aspect of the present disclosure provides an APAP-protein adduct for diagnosing acetaminophen-induced toxicity. According to the present disclosure, the inventors have identified proteins that are modified by N-acetyl-pbenzoquinoneimine (NAPQI) in subjects with acetaminophen-induced toxicity. Non-limiting examples of proteins modified by NAPQI include betaine-homocysteine 5-methyltransferase 1, cytoplasmic aspartate aminotransferase, 1,4-alpha-glucan branching enzyme, formimidoyltransferase-cyclodeaminase, and dystrophin.
2 Citations
11 Claims
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1. (canceled)
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2. (canceled)
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3. A method for measuring the amount of acetaminophen-protein adduct in a biological sample, the method comprising:
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a) obtaining a biological sample from a subject; and b) measuring the amount of acetaminophen-protein adduct in the sample by detecting one or more APAP-protein adducts, wherein each APAP-protein adduct comprises a protein modified with NAPQI, and wherein the protein is selected from the group consisting of betaine-homocysteine S-methyltransferase 1, cytoplasmic aspartate aminotransferase, 1,4-alpha-glucan-branching enzyme, formimidoyltransferase-cyclodeaminase, or dystrophin. - View Dependent Claims (4)
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5. A method of detecting acetaminophen-induced toxicity in a subject, the method comprising:
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a) obtaining a biological sample from the subject; b) measuring the amount of acetaminophen-protein adduct in the sample by detecting one or more APAP-protein adducts, wherein each APAP-protein adduct comprises a protein modified with NAPQI, and wherein the protein is selected from the group consisting of betaine-homocysteine S-methyltransferase 1, cytoplasmic aspartate aminotransferase, 1,4-alpha-glucan-branching enzyme, formimidoyltransferase-cyclodeaminase, or dystrophin; and c) comparing the amount of acetaminophen-protein adduct in the sample to a reference value, wherein a greater amount of acetaminophen-protein adduct in the sample compared to the reference value indicates acetaminophen-induced toxicity in the subject. - View Dependent Claims (6, 7, 8, 9)
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10. (canceled)
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11. A method of detecting acetaminophen-induced toxicity in a subject, the method comprising:
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a) obtaining a sample from the subject; b) measuring the amount of acetaminophen-protein adduct in the sample to determine a profile of APAP-protein adducts in the subject, the profile comprising the identity and concentration in the sample from the subject of one or more APAP-protein adducts, wherein each APAP-protein adduct comprises a protein modified with NAPQI, and wherein the protein is selected from the group consisting of betaine-homocysteine S-methyltransferase 1, cytoplasmic aspartate aminotransferase, 1,4-alpha-glucan-branching enzyme, formimidoyltransferase-cyclodeaminase, or dystrophin; c) comparing the profile determined in (b) to a database comprising the presence and concentration of one or more APAP-protein adducts correlated with acetaminophen toxicity; d) identifying a matching entry of the database in which the identity and concentration of the one or more APAP-protein adducts matches the identity and concentration of the one or more APAP-protein adducts in the sample; and e) determining the acetaminophen toxicity comprising the particular acetaminophen toxicity of the matching entry.
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Specification