Document Detail


Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heart.
MedLine Citation:
PMID:  24472606     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Mercury exposure is associated with increased risk of cardiovascular disease and profound cardiotoxicity. However, the correlation between Hg(2+)-mediated toxicity and alteration in cardiac cytochrome P450s (Cyp) and their dependent arachidonic acid metabolites has never been investigated. Therefore, we investigated the effect of acute mercury toxicity on the expression of Cyp-epoxygenases and Cyp-ω-hydroxylases and their associated arachidonic acid metabolites in mice hearts. In addition, we examined the expression and activity of soluble epoxide hydrolase (sEH) as a key player in arachidonic acid metabolism pathway. Mercury toxicity was induced by a single intraperitoneal injection (IP) of 2.5mg/kg of mercuric chloride (HgCl2). Our results showed that mercury treatment caused a significant induction of the cardiac hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP); in addition to Cyp1a1, Cyp1b1, Cyp2b9, Cyp2b10, Cyp2b19, Cyp2c29, Cyp2c38, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f15, Cyp4f16 and Cyp4f18 gene expression. Moreover, Hg(2+) significantly increased sEH protein expression and activity levels in hearts of mercury-treated mice, with a consequent decrease in 14,15-, and 11,12-epoxyeicosatrienoic acids (EETs) levels. Whereas the formation of 14,15-, 11,12-, 8,9-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. In conclusion, acute Hg(2+) toxicity modulates the expression of several Cyp and sEH enzymes with a consequent decrease in the cardioprotective EETs which could represent a novel mechanism by which mercury causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent Hg(2+)-induced hypertrophy.
Authors:
Issa E A Amara; Osama H Elshenawy; Mohamed Abdelrady; Ayman O S El-Kadi
Related Documents :
1536516 - Organic acids interfere in the measurement of carbon dioxide concentration by the kodak...
8799296 - 3-, 6- and 7-hydroxyoctanoic acids are metabolites of medium-chain triglycerides and ex...
8406236 - Metabolism and pharmacokinetics of deuterium-labelled di-2-(ethylhexyl) adipate (deha) ...
22934026 - Omega 3 fatty acid inhibition of inflammatory cytokine-mediated connexin43 regulation i...
3099336 - Modulation of the 5-lipoxygenase activity of mc-9 mast cells: activation by hydroperoxi...
14989486 - Application of tetraoxadiaza-crown ether derivatives as chiral selector modifiers in ca...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-25
Journal Detail:
Title:  Toxicology letters     Volume:  -     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ireland Ltd.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Genome-wide miRNA-profiling of Aflatoxin B1-induced hepatic injury using deep sequencing.
Next Document:  The NF-?B family member RelB regulates microRNA miR-146a to suppress cigarette smoke-induced COX-2 p...