Paraoxonase 1 Activity in Subchronic Low-Level Inorganic Arsenic Exposure Through Drinking Water Olusegun K. Afolabi, 1,2 Adedoja D. Wusu, 1,3 Olufunmilayo O. Ogunrinola, 1,3 Esther O. Abam, 1 David O. Babayemi, 1 Oluwatosin A. Dosumu, 1 Okechukwu B. Onunkwor, 1 Elizabeth A. Balogun, 1,4 Olusegun O. Odukoya, 5 Oladipo Ademuyiwa 1 1 Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria 2 Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomosho, Nigeria 3 Department of Biochemistry, Lagos State University, Ojoo, Nigeria 4 Department of Biochemistry, University of Ilorin, Nigeria 5 Department of Chemistry, Federal University of Agriculture, Abeokuta, Nigeria Received 25 February 2014; revised 12 July 2014; accepted 13 July 2014 ABSTRACT: Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic, epidemiological studies indicate a role for paraoxonase 1 (PON1) in cardiovascular diseases. To investigate the association between inorganic arsenic exposure and cardiovascular diseases, rats were exposed to sodium arsenite (trivalent; 50, 100, and 150 ppm As) and sodium arsenate (pentavalent; 100, 150, and 200 ppm As) in their drinking water for 12 weeks. PON1 activity towards paraoxon (PONase) and phenylacetate (AREase) in plasma, lipoproteins, hepatic, and brain micro- somal fractions were determined. Inhibition of PONase and AREase in plasma and HDL characterized the effects of the two arsenicals. While the trivalent arsenite inhibited PONase by 33% (plasma) and 46% (HDL), respectively, the pentavalent arsenate inhibited the enzyme by 41 and 34%, respectively. AREase activity was inhibited by 52 and 48% by arsenite, whereas the inhibition amounted to 72 and 67%, respectively by arsenate. The pattern of inhibition in plasma and HDL indicates that arsenite induced a dose-dependent inhi- bition of PONase whereas arsenate induced a dose-dependent inhibition of AREase. In the VLDL 1 LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microso- mal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pro- nounced in the hepatic microsomes where a 70% inhibition was observed at the highest dose of pentavalent arsenic. Microsomal cholesterol was increased by the two arsenicals resulting in increased cho- lesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic expo- sure may be an incipient biochemical event in the cardiovascular effects of arsenic. Modulation of PON1 activity by arsenic may also be mediated through changes in membrane fluidity brought about by changes in the concentration of cholesterol in the microsomes. V C 2014 Wiley Periodicals, Inc. Environ Toxicol 00: 000–000, 2014. Keywords: paraoxonase; arsenic exposure; drinking water Correspondence to: O. Ademuyiwa; e-mail: adelad2@yahoo.com Conflicts of Interest: The authors declare that there are no conflicts of interest. Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/tox.22030 V C 2014 Wiley Periodicals, Inc. 1