alexa Mechanism of protection of ebselen against paracetamol-induced toxicity in rat hepatocytes.
Business & Management

Business & Management

Journal of Business & Financial Affairs

Author(s): Li QJ, Bessems JG, Commandeur JN, Adams B, Vermeulen NP

Abstract Share this page

Abstract The protective effect of ebselen (PZ 51), an anti-inflammatory agent, on paracetamol-induced (1 mM) cytotoxicity in hepatocytes freshly isolated from beta-naphthoflavone-pretreated rats was studied. At a concentration of 50 microM added simultaneously with paracetamol, ebselen prevented paracetamol-induced leakage of lactate dehydrogenase (LDH) almost completely and lipid peroxidation (LPO) and depletion of glutathione (GSH) substantially. These protective effects were even more pronounced at 100 microM concentration of ebselen. When added to the hepatocytes 1 hr before paracetamol, 50 microM of ebselen also prevented LDH leakage, LPO and GSH depletion. Reverse addition of paracetamol and ebselen did not result in protection. Simultaneous incubation of 100 microM ebselen and paracetamol inhibited GSH conjugation of paracetamol by more than 50\%, however, without any effect on glucuronidation and sulfation of paracetamol. Ebselen was shown not to react directly with paracetamol nor to inhibit cytochrome P450 activity measured as 7-ethoxycoumarin O-deethylase (ECD) activity in the hepatocytes. At mixing, synthetic ebselen selenol and synthetic N-acetyl-p-benzoquinone imine (NAPQI) were shown to form paracetamol and ebselen diselenide. No indication was found for the formation of an ebselen-paracetamol conjugate upon reacting synthetic NAPQI and synthetic ebselen selenol. Reduction of NAPQI, the reactive metabolite of paracetamol, by ebselen selenol is discussed in terms of the mechanism of cytoprotection.
This article was published in Biochem Pharmacol and referenced in Journal of Business & Financial Affairs

Relevant Expert PPTs

Relevant Speaker PPTs

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]micsonline.com

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords