title: Arsenic-induced dyslipidemia in male albino rats: comparison between trivalent and pentavalent inorganic arsenic in drinking water.
abstract: BACKGROUND
  Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. However, the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic.
  
  
  METHODS
  In order to investigate the effects of inorganic arsenic exposure on lipid metabolism, male albino rats were exposed to 50, 100 and 150 ppm arsenic as sodium arsenite and 100, 150 and 200 ppm arsenic as sodium arsenate respectively in their drinking water for 12 weeks.
  
  
  RESULTS
  Dyslipidemia induced by the two arsenicals exhibited different patterns. Hypocholesterolemia characterised the effect of arsenite at all the doses, but arsenate induced hypercholesterolemia at the 150 ppm As dose. Hypertriglyceridemia was the hallmark of arsenate effect whereas plasma free fatty acids (FFAs) was increased by the two arsenicals. Reverse cholesterol transport was inhibited by the two arsenicals as evidenced by decreased HDL cholesterol concentrations whereas hepatic cholesterol was increased by arsenite (100 ppm As), but decreased by arsenite (150 ppm As) and arsenate (100 ppm As) respectively. Brain cholesterol and triglyceride were decreased by the two arsenicals; arsenate decreased the renal content of cholesterol, but increased renal content of triglyceride. Arsenite, on the other hand, increased the renal contents of the two lipids. The two arsenicals induced phospholipidosis in the spleen. Arsenite (150 ppm As) and arsenate (100 ppm As) inhibited hepatic HMG CoA reductase. At other doses of the two arsenicals, hepatic activity of the enzyme was up-regulated. The two arsenicals however up-regulated the activity of the brain enzyme. We observed positive associations between tissue arsenic levels and plasma FFA and negative associations between tissue arsenic levels and HDL cholesterol.
  
  
  CONCLUSIONS
  Our findings indicate that even though sub-chronic exposure to arsenite and arsenate through drinking water produced different patterns of dyslipidemia, our study identified two common denominators of dyslipidemia namely: inhibition of reverse cholesterol transport and increase in plasma FFA. These two denominators (in addition to other individual perturbations of lipid metabolism induced by each arsenical), suggest that in contrast to strengthening a dose-dependent effect phenomenon, the two forms of inorganic arsenic induced lipotoxic and non-lipotoxic dyslipidemia at "low" or "medium" doses and these might be responsible for the cardiovascular and other disease endpoints of inorganic arsenic exposure through drinking water.
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. segunII@yahoo.com.|Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomosho, Nigeria. segunII@yahoo.com.
authors.forename: Olusegun K
authors.initials: OK
authors.lastname: Afolabi
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. dorcaswusu@yahoo.com.|Department of Biochemistry, Lagos State University, Ojoo, Lagos, Nigeria. dorcaswusu@yahoo.com.
authors.forename: Adedoja D
authors.initials: AD
authors.lastname: Wusu
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. ooogunrinola@yahoo.com.|Department of Biochemistry, Lagos State University, Ojoo, Lagos, Nigeria. ooogunrinola@yahoo.com.
authors.forename: Olabisi O
authors.initials: OO
authors.lastname: Ogunrinola
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. estherabam@rocketmail.com.|Biochemistry Unit, Department of Chemical Sciences, Bells University of Technology, Ota, Nigeria. estherabam@rocketmail.com.
authors.forename: Esther O
authors.initials: EO
authors.lastname: Abam
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. davidbabayemi@gmail.com.
authors.forename: David O
authors.initials: DO
authors.lastname: Babayemi
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. atdos2003@yahoo.co.uk.
authors.forename: Oluwatosin A
authors.initials: OA
authors.lastname: Dosumu
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. benolevite@yahoo.co.uk.
authors.forename: Okechukwu B
authors.initials: OB
authors.lastname: Onunkwor
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. ea_balogun@yahoo.com.|Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. ea_balogun@yahoo.com.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Balogun
authors.affiliation: Department of Chemistry, Federal University of Agriculture, Abeokuta, Nigeria. ooodukoya@yahoo.com.
authors.forename: Olusegun O
authors.initials: OO
authors.lastname: Odukoya
authors.affiliation: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria. adelad2@yahoo.com.
authors.forename: Oladipo
authors.initials: O
authors.lastname: Ademuyiwa
mesh_terms: D000818:Animals; D001149:Arsenates / Q000493:pharmacokinetics / Q000633:toxicity*; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000737:chemistry*; D050171:Dyslipidemias / Q000139:chemically induced* / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017670:Sodium Compounds / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D001149:Arsenates; D018053:Arsenites; D060766:Drinking Water; D008055:Lipids; D008074:Lipoproteins; D017670:Sodium Compounds; C017947:sodium arsenite; C009277:sodium arsenate; D006903:Hydroxymethylglutaryl CoA Reductases