Acetaminophen-NAPQI Hepatotoxicity: A Cell Line Model …
Acetaminophen hepatotoxicity is mediated by the reactive metabolite N-acetyl-p-benzoquinonimine (NAPQI). We performed a “discovery” genome-wide association study using a cell line–based model system to study the possible …
The biochemistry of acetaminophen hepatotoxicity and rescue: a ...
Acetaminophen (N-acetyl-para-aminophenol) is the most widely used over-the-counter or prescription painkiller in the world. Acetaminophen is metabolized in the liver where a toxic byproduct is produced that can be removed by conjugation with glutathione.
NAPQI - Wikipedia
In an average adult, only a small amount (approximately 10% of a therapeutic paracetamol dose) of NAPQI is produced, which is inactivated by conjugation with glutathione (GSH). The amount of NAPQI produced differs in certain populations.
N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated …
We report (i) direct detection of NAPQI formed as an oxidation product of acetaminophen by cytochrome P-450 and cumene hydroperoxide and (ii) indirect evidence that is compelling for NAPQI formation from acetaminophen by cytochrome P-450, NADPH, and NADPH-cytochrome P-450 reductase.
Mechanisms of N-acetyl-p-benzoquinone imine cytotoxicity
N-Acetyl-p-benzoquinone imine (NAPQI), a reactive metabolite of acetaminophen, rapidly reacts at physiological pH with glutathione (GSH) forming an acetaminophen-glutathione conjugate and stoichiometric amounts of acetaminophen and glutathione disulfide (GSSG).
N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen …
2004年3月30日 · NAPQI strongly impaired the ability of topoisomerase IIalpha to reseal cleaved DNA molecules, suggesting that inhibition of DNA religation is the primary mechanism underlying cleavage enhancement.
The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI …
NAPQI binds covalently to GS causing irreversible enzyme inhibition in vitro. This is an important novel biochemical observation. It is the first indication that NAPQI may inhibit glutathione synthesis, which is pivotal in NAPQI detoxification.
Acetaminophen Toxicity: Novel Insights Into Mechanisms and …
A minor component is acted upon by cytochrome P450 enzymes such as Cyp2E1 and Cyp1A2 to form a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI)8. Though highly reactive, NAPQI is rarely harmful after consumption of therapeutic doses because it is rapidly conjugated with abundant glutathione stores in the liver and excreted through the ...
The biochemistry of acetaminophen hepatotoxicity and rescue: a ...
2012年12月19日 · The mathematical model provides a new tool for studying the effects of various doses of acetaminophen on the liver metabolism of acetaminophen and glutathione. It can be used to study how the metabolism of acetaminophen depends on …
Metabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine
2022年6月24日 · After overdose, protein adducts form when APAP oxidizes to form the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). NAPQI overwhelms glutathione supply and the unbound NAPQI quickly binds to cysteine residues in hepatocytes to produce APAP-cys protein adducts.