The inhibitory effect of acetaminophen on the myeloperoxidase-induced antimicrobial system of the polymorphonuclear leukocyte

Zyl, Johann M. van; Basson, Karen; Walt, B. J. Van Der

doi:10.1016/0006-2952(89)90163-9

Cited by 23 publications

(3 citation statements)

References 31 publications

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“…The H 2 O 2 -dependent MPO-catalyzed polymerization products of acetaminophen; however, acetaminophen can compete effectively with Cl À as MPO substrate and thus HOCl formation is suppressed; while HOCl, nevertheless present, can be scavenged by the drug. In this way, the microbicidal action of the MPO H 2 O 2 -Cl À system can be seriously limited in the presence of high concentrations of acetaminophen (Van Zyl et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective effect of Caesalpinia gilliesii and Cajanus cajan proteins against acetoaminophen overdose-induced hepatic damage

et al. 2014

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This study aims to evaluate two proteins derived from the seeds of the plants Cajanus cajan (Leguminosae) and Caesalpinia gilliesii (Leguminosae) for their abilities to ameliorate the toxic effects of chronic doses of acetoaminphen (APAP) through the determination of certain biochemical parameters including liver marker enzymes: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Also, total protein content and hepatic marker enzyme, lactate dehydrogenase were studied. Moreover, liver antioxidants, glutathione (GSH), nitric oxide, and lipid peroxides were determined in this study. Hepatic adenosine triphosphatase (ATPase), adenylate energy charge (ATP, adenosine diphosphate, adenosine monophosphate, and inorganic phosphate), and phosphate potential, serum interleukin-6, tumor necrosis factor-α, and myeloperoxidase were also examined in the present study. On the other hand, histopathological examination of intoxicated and liver treated with both proteins was taken into consideration. The present results show disturbances in all biochemical parameters and hepatic toxicity signs including mild vascular congestion, moderate inflammatory changes with moderate congested sinusoids, moderate nuclear changes (pyknosis), moderate centrilobular necrosis, fatty changes, nuclear pyknosis vascular congestion, and change in fatty centrilobular necrosis liver. Improvement in all biochemical parameters studied was noticed as a result of treatment intoxicated liver with C. gilliesii and C. cajan proteins either paracetamol with or post paracetamol treatment. These results were documented by the amelioration signs in rat's hepatic architecture. Thus, both plant protein extracts can upregulate and counteract the inflammatory process, minimize damage of the liver, delay disease progression, and reduce its complications.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective effect of Caesalpinia gilliesii and Cajanus cajan proteins against acetoaminophen overdose-induced hepatic damage

et al. 2014

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“…Mitchell and colleagues showed that, whilst the major routes of biotransformation for APAP are indeed detoxication reactions, that form the phenolic sulfate and glucuronide conjugates, a minor route was the oxidative metabolism of the drug via the P450 system to an electrophilic intermediate, most likely N-acetyl-p-benzoquinoneimine (NAPQI, also commonly termed NABQI), which rapidly depleted hepatic glutathione (GSH). 5 Subsequently, it was shown that acetaminophen can be activated by non-P450-dependent metabolism, for example by cyclooxygenases 6 and myeloperoxidases, 7 although the contribution of this to the toxicity of APAP is unclear. When intracellular GSH concentrations reached a low level, toxicity ensued.…”

Section: Introductionmentioning

confidence: 99%

Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective

Athersuch

Antoine

Boobis

et al. 2018

Toxicology Research

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After over 60 years of therapeutic use in the UK, paracetamol (acetaminophen, -acetyl--aminophenol, APAP) remains the subject of considerable research into both its mode of action and toxicity. The pharmacological properties of APAP are the focus of some activity, with the role of the metabolite -arachidonoylaminophenol (AM404) still a topic of debate. However, that the hepatotoxicity of APAP results from the production of the reactive metabolite-acetyl--benzoquinoneimine (NAPQI/NABQI) that can deplete glutathione, react with cellular macromolecules, and initiate cell death, is now beyond dispute. The disruption of cellular pathways that results from the production of NAPQI provides a source of potential biomarkers of the severity of the damage. Research in this area has provided new diagnostic markers such as the microRNA miR-122 as well as mechanistic biomarkers associated with apoptosis, mitochondrial dysfunction, inflammation and tissue regeneration. Additionally, biomarkers of, and systems biology models for, glutathione depletion have been developed. Furthermore, there have been significant advances in determining the role of both the innate immune system and genetic factors that might predispose individuals to APAP-mediated toxicity. This perspective highlights some of the progress in current APAP-related research.

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“…2 The oxygen reactive metabolites may be considered to play a major role in the microbicidal action of PMNs.~ The analgesic and antipyretic drug, acetaminophen (AM, N-acetyl-paminophenol) binds to purified myeloperoxidase (MPO) via its acetamido side chain and paralyses the MPO-H2O2-C1-antimicrobial system of PMNs. 4 Furthermore, AM is capable of inhibiting superoxide anion generation and the degradation of PMNS.~ In a recent study conducted in this laboratory, AM exerted a marked inhibitory effect on the ability of isolated human PMNs to generate OFRs upon stimulation with the soluble agent, phorbol myristate acetate (PMA). Also, AM exerted some inhibitory effect on the ability of PMNs to generate superoxide anions and to phagocytose opsonized dead yeast cells in a dose-dependent fashion.…”

Section: Introductionmentioning

confidence: 99%

The Thermal Potentiation of Acetaminophen-Inhibited PMN Oxidative Metabolismin Vitro

Shalabi

Al-Tuwaijri

1996

Biopharm. Drug Dispos.

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The effect of high temperatures (39, 41, and 43 °C) on acetaminophen (AM‐) induced inhibition of the oxidative respiratory burst of polymorphonuclear leukocytes (PMNs) in vitro has been examined. Whole blood or isolated human PMNs were exposed to various temperatures in vitro in the presence or absence of AM for 0–90 min. Phagocyte membrane‐bound NADPH oxidase was studied using the luminol chemiluminescence (CL) response and the superoxide dismutase inhibitable reduction of ferricytochrome C. The NADPH oxidase was stimulated by phorbol myristate acetate (PMA). The results showed that high temperatures (39–43 °C) potentiate the AM inhibitory effect on CL peak response of phagocytes in a temperature‐dependent manner. Furthermore, the inhibition of superoxide (O−2) production induced by AM was potentiated by incubating the cells at 39 or 43 °C at different time intervals. These studies suggest that high temperatures significantly potentiate the AM inhibitory effect on oxidative metabolism of PMNs in vitro. These actions of AM may influence the outcome in patients with infectious febrile conditions.

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The inhibitory effect of acetaminophen on the myeloperoxidase-induced antimicrobial system of the polymorphonuclear leukocyte

Cited by 23 publications

References 31 publications

Hepatoprotective effect of Caesalpinia gilliesii and Cajanus cajan proteins against acetoaminophen overdose-induced hepatic damage

Hepatoprotective effect of Caesalpinia gilliesii and Cajanus cajan proteins against acetoaminophen overdose-induced hepatic damage

Paracetamol metabolism, hepatotoxicity, biomarkers and therapeutic interventions: a perspective

The Thermal Potentiation of Acetaminophen-Inhibited PMN Oxidative Metabolismin Vitro

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