Document Detail

Acute arsenic toxicity alters cytochrome P450 and soluble epoxide hydrolase and their associated arachidonic acid metabolism in C57Bl/6 mouse heart.
MedLine Citation:
PMID:  22680237     Owner:  NLM     Status:  Publisher    
Acute arsenic (As(III)) exposure has been reported to cause cardiac toxicity, however this toxicity was never linked to the disturbance in cytochrome P450 (P450)-mediated arachidonic acid metabolism. Therefore, we investigated the effect of acute As(III) toxicity on the expression of P450 and soluble epoxide hydrolase (sEH) and their associated arachidonic acid metabolism in mice hearts. As(III) toxicity was induced by a single intraperitoneal injection of 12.5 mg/kg of As(III). Our results showed that As(III) treatment caused a significant induction of the cardiac hypertrophic markers in addition to Cyp1b1, Cyp2b, Cyp2c, Cyp4f, and sEH gene expression in mice hearts. Furthermore, As(III) increased sEH protein expression and activity in hearts with a consequent decrease in 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) formation. Whereas the formation of 8,9-, 11,12-, 14,15-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. As(III) also increased sEH mRNA and protein expression levels in addition to the hypertrophic markers which was reversed by knockdown of sEH in H9c2 cells. In conclusion, acute As(III) toxicity alters the expression of several P450s and sEH enzymes with a consequent decrease in the cardioprotective EETs which may represent a novel mechanism by which As(III) causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent As(III)-induced hypertrophy.
Anwar Anwar-Mohamed; Ahmed A El-Sherbeni; Seok H Kim; Hassan N Althurwi; Beshay N M Zordoky; Ayman O S El-Kadi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-9
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  -     ISSN:  1366-5928     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta , Edmonton, Alberta , Canada.
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