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 (12.5mg/kg) altered CYP epoxygenases, CYP ω-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.
Bibliographical noteFunding Information:
This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN 250139-07 to A.O.S. A.A.-M. is the recipient of Alberta Innovates Technology Futures Scholarship, and Izaak Walton Killam memorial graduate scholarship. A.A.E. is the recipient of Egyptian Government Scholarship. S.H.K. is the recipient of Alberta Innovates Health Solutions summer studentship. H.N.A. is the recipient of the Kingdom of Saudi Arabia government Scholarship. O.H.E. is the recipient of University of Alberta recruitment scholarship. B.N.M.Z. is the recipient of Health Solutions Scholarship.
- 20-hydroxyeicosatetraenoic acid
- Cytochrome epoxygenases
- Cytochrome ω-hydroxylases
- Epoxyeicosatrienoic acid
- Soluble epoxide hydrolase