title: Paraoxonase 1 activity in subchronic low-level inorganic arsenic exposure through drinking water.
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 microsomal 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 inhibition of PONase whereas arsenate induced a dose-dependent inhibition of AREase. In the VLDL + LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microsomal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pronounced 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 cholesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic exposure 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.
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.|Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomosho, Nigeria.
authors.forename: Olusegun K
authors.initials: OK
authors.lastname: Afolabi
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.|Department of Biochemistry, Lagos State University, Ojoo, Nigeria.
authors.forename: Adedoja D
authors.initials: AD
authors.lastname: Wusu
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.|Department of Biochemistry, Lagos State University, Ojoo, Nigeria.
authors.forename: Olufunmilayo O
authors.initials: OO
authors.lastname: Ogunrinola
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
authors.forename: Esther O
authors.initials: EO
authors.lastname: Abam
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
authors.forename: David O
authors.initials: DO
authors.lastname: Babayemi
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
authors.forename: Oluwatosin A
authors.initials: OA
authors.lastname: Dosumu
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
authors.forename: Okechukwu B
authors.initials: OB
authors.lastname: Onunkwor
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.|Department of Biochemistry, University of Ilorin, Nigeria.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Balogun
authors.affiliation: Department of Chemistry, Federal University of Agriculture, Abeokuta, Nigeria.
authors.forename: Olusegun O
authors.initials: OO
authors.lastname: Odukoya
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
authors.forename: Oladipo
authors.initials: O
authors.lastname: Ademuyiwa
mesh_terms: D000818:Animals; D001152:Arsenicals; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000032:analysis; D007306:Insecticides / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010261:Paraoxon / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D001152:Arsenicals; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D060766:Drinking Water; D007306:Insecticides; D010648:Phenylacetates; D014874:Water Pollutants, Chemical; C572204:Pon1 protein, rat; D043303:Aryldialkylphosphatase; C025136:phenylacetic acid; D010261:Paraoxon
keywords: arsenic exposure; drinking water; paraoxonase