Journal
XENOBIOTICA
Volume 43, Issue 8, Pages 719-729Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/00498254.2012.754113
Keywords
Arsenite; cytochrome epoxygenases; cytochrome omega-hydroxylases; epoxyeicosatrienoic acid; soluble epoxide hydrolase; 20-hydroxyeicosatetraenoic acid
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN 250139-07]
- Alberta Innovates Technology Futures Scholarship
- Izaak Walton Killam memorial graduate scholarship
- Egyptian Government
- Alberta Innovates Health Solutions
- Kingdom of Saudi Arabia government Scholarship
- University of Alberta
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1. Arsenic (As(III)) toxicity has received increasing attention as human exposure to arsenic is associated with pulmonary, hepatic and renal toxicities. Therefore, in the present study, we investigated the effect of acute As(III) treatment on pulmonary, hepatic and renal cytochrome (CYP) P450-mediated arachidonic acid metabolism. 2. Our results demonstrated that acute As(III) treatment (12.5 mg/kg) altered CYP epoxygenases, CYP omega-hydroxylases and EPHX2 mRNA levels that were isozyme and tissue specific. 3. Furthermore, As(III) increased the formation of epoxyeicosatrienoic acids (EETs) in the kidney without affecting their levels in the lung or liver. In addition, acute As(III) treatment increased dihydroxyeicosatrienoic acid (DHETs) formation in the lung, while it did not affect liver DHETs formation and decreased kidney DHETs formation. 4. As(III) also increased total epoxygenases activity in the lung while it decreased its levels in the kidney and had no effect on the liver. Furthermore, As(III) increased 20-hydroxyeicosatetraenoic acid formation in the liver while it decreased its formation in the kidney. 5. Lastly, As(III) increased soluble epoxide hydrolase activity in the lung, while it decreased its levels in the kidney and had no effect on the liver. In conclusion, this is the first demonstration that As(III) alters arachidonic acid metabolism in a tissue specific manner.
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