Search results for "ACETAMINOPHEN"
showing 10 items of 44 documents
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
2014
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in larg…
The potential of acetaminophen as a prodrug in gene-directed enzyme prodrug therapy.
2000
Acetaminophen is oxidized by human CYP1A2 to the cytotoxic metabolite N-acetylbenzoquinoneimine (NABQI). Incubation of cells transfected with human CYP1A2 (H1A2 MZ cells) with 4-20 mM acetaminophen for 6 hours at 37 degrees C caused extensive cytotoxicity (cell viability10%). In contrast, nontransfected V79 MZ cells were unaffected (viability95%). By mixing H1A2 MZ cells with V79 MZ cells in various proportions and incubating with 4 mM acetaminophen, it was shown that the NABQI released from H1A2 MZ cells also caused cytotoxicity of bystander cells. Thus, in a mixture containing 5% H1A2 MZ cells, exposure to 4 mM acetaminophen for 6 hours resulted in complete cell killing by 24 hours. A sim…
Flow-Injection Spectrophotometric Determination of Phenolic Drugs and Carbamate Pesticides by Coupling with Diazotized 2,4,6-Trimethylaniline
1999
Abstract A flow-injection (FI) spectrophotometric system is proposed for the determination of phenols and carbamates. In the FI manifolds, the solutions of phenols or carbamates (the latter after hydrolysis with NaOH) were injected into a diazonium ion carrier stream at pH 9.5 (buffered with tetrahydroborate), which was formed by mixing 2,4,6-trimethylaniline (TMA) with nitrate in a sodium dodecyl sulfate aqueous micellar medium. Absorbance was measured at 550 nm. The system combines the advantages derived from the use of TMA for the coupling of phenols in basic micellar media, because of the inhibition of the self-coupling reaction of the reagent, with the precision and speed of the FI pro…
Comparison of the efficacy of low doses of methylprednisolone, acetaminophen, and dexketoprofen trometamol on the swelling developed after the remova…
2015
WOS: 000365269900016
Deep dry needling of trigger points located in the lateral pterygoid muscle: efficacy and safety of treatment for management of myofascial pain and t…
2014
Background To determine whether deep dry needling (DDN) of trigger points (TPs) in the lateral pterygoid muscle (LPM) would significantly reduce pain and improve function, compared with methocarbamol/paracetamol medication. Material and Methods Forty-eight patients with chronic myofascial pain located in the LPM were selected and randomly assigned to one of two groups (DDN test group, n=24; drug-treated control group, n=24). The test group received three applications of needling of the LPM once per week for three weeks, while control group patients were given two tablets of a methocarbamol/paracetamol combination every six hours for three weeks. Assessments were carried out pretreatment, 2 …
An experimental design for the controlled modulation of intracellular GSH levels in cultured hepatocytes
2006
This work proposes a practical experimental approach that allows the rapid in situ generation of a wide range of intracellular GSH concentrations in the intact hepatocyte under highly reproducible conditions. The strategy involves the use of diethyl maleate, a thiol-reactive electrophile that causes rapid and extensive GSH depletion, as well as GSH monoethylester, a GSH analogue that is readily taken up by cells and deesterified intracellularly to render GSH. For both agents, we have analyzed (i) the minimal exposure time required to produce a maximal and dose-related effect on intracellular GSH without altering hepatocyte viability or subsequent survival in culture, and (ii) the relative s…
A Model‐Based Workflow to Benchmark the Clinical Cholestasis Risk of Drugs
2021
We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes in expression levels of genes involved in the enterohepatic circulation of bile acids were obtained from an in vitro assay mimicking 14 days of repeated drug administration for 10 marketed drugs. These changes in gene expression over time were contextualized in a physiology-based bile acid model of glycochenodeoxycholic acid. The simulated drug-induced response in bile acid concentrations was then scaled with the applied drug doses to calculate the cholestatic potential for each compound. A ranking of the cholest…
Paracetamol and antibiotics in childhood and subsequent development of wheezing/asthma: association or causation?
2011
Background Several studies found an association between early administration of paracetamol and antibiotics and development of wheezing. This could be due to confounding: wheeze and asthmatic symptoms in early childhood are difficult to distinguish from respiratory tract infections that are widely treated with these drugs; in case of persistence of symptoms up to school age, this could explain the observed relationship. Methods We investigated the association between paracetamol and antibiotics use in the first year of life and wheezing phenotypes, i.e. wheezing starting in different time periods (early, persistent and late-onset) in the SIDRIA-2 study, a cross-sectional survey of 16,933 ch…
Molecular mechanisms of Id2 down-regulation in rat liver after acetaminophen overdose. Protection by N-acetyl-L-cysteine.
2010
Id2 is a pleiotropic protein whose function depends on its expression levels. Id2-deficient cells show increased cell death. This study explored the molecular mechanisms for the modulation of Id2 expression elicited by GSH and oxidative stress in the liver of acetaminophen (APAP)-intoxicated rats. APAP-overdose induced GSH depletion, Id2 promoter hypoacetylation, RNApol-II released and, therefore, Id2 down-regulation. Id2 expression depends on c-Myc binding to its promoter. APAP-overdose decreased c-Myc content and binding to Id2 promoter. Reduction of c-Myc was not accompanied by decreased c-myc mRNA, suggesting a mechanism dependent on protein stability. Administration of N-acetyl-cystein…
Sudden severe abdominal pain after a single low dose of paracetamol/codein in a cholecystectomized patient: learning from a case report.
2009
We report the case of an elderly patient with diastolic heart failure and renal insufficiency admitted to hospital as he complained of having a history of hypogastric pain and dysuria without fever due to renal lithiasis and urinary infection. Because the pain was persistence, and considering the presence of renal dysfunction, it was administered a single low dose of paracetamol/codein (500/30 mg). After about 1 hour of the administration, he suddenly complained of the onset of a lancinating epigastric pain radiating to the whole abdomen and retrosternum accompanied by nausea. The electrocardiogram (EKG) was negative for myocardial infarction and computed tomography excluded aortic dissecti…