Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS
Joint Authors
Trettin, Arne
Böhmer, Anke
Suchy, Maria-Theresia
Probst, Irmelin
Staerk, Ulrich
Stichtenoth, Dirk O.
Frölich, Jürgen C.
Tsikas, Dimitrios
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-03-31
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Paracetamol (acetaminophen) is a widely used analgesic drug.
It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS).
We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol.
Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively.
Endothelial NO synthesis was assessed by measuring nitrite in plasma.
Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress.
Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity.
Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged.
Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation.
This effect may be antagonized by increasing endothelial NO synthesis.
High-dosed paracetamol did not increase oxidative stress.
At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes.
We conclude that paracetamol does not increase oxidative stress in humans.
American Psychological Association (APA)
Trettin, Arne& Böhmer, Anke& Suchy, Maria-Theresia& Probst, Irmelin& Staerk, Ulrich& Stichtenoth, Dirk O.…[et al.]. 2014. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS. Oxidative Medicine and Cellular Longevity،Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-1046967
Modern Language Association (MLA)
Trettin, Arne…[et al.]. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS. Oxidative Medicine and Cellular Longevity No. 2014 (Dec. 2014), pp.1-12.
https://search.emarefa.net/detail/BIM-1046967
American Medical Association (AMA)
Trettin, Arne& Böhmer, Anke& Suchy, Maria-Theresia& Probst, Irmelin& Staerk, Ulrich& Stichtenoth, Dirk O.…[et al.]. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS. Oxidative Medicine and Cellular Longevity. 2014. Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-1046967
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1046967