title: The effects of atorvastatin on oxidative stress in L-NAME-treated rats.
abstract: OBJECTIVE
  Current evidence suggests that the beneficial vascular effects of statins are not limited to the statins' lipid-lowering properties; these drugs can also improve vascular endothelial cell function. Nω-nitro-l-arginine methyl ester (L-NAME) is a potent synthetic nitric oxide inhibitor, and long-term oral L-NAME treatment is used to induce vascular lesions in experimental animal models.
  
  
  METHODS
  We determined the effects of statins on protein carbonyl (PCO), lipid hydroperoxides (LHP), oxidized low-density lipoproteins (ox-LDL) and antioxidants such as paraoxonase 1 (PON1) and total thiols (T-SH) in long-term L-NAME-treated rats. Adult male Wistar rats were divided into three groups, namely, control, L-NAME-treated (1 mg/mL in drinking water for three weeks), and atorvastatin plus L-NAME-treated (4 mg/kg/day atorvastatin for 1 week during the third week of L-NAME treatment) groups.
  
  
  RESULTS
  In the L-NAME group, the ox-LDL, LHP and PCO were higher and the PON1 and T-SH were lower than the concentrations observed for the controls. When compared with the L-NAME group, the L-NAME plus atorvastatin group had significantly lower ox-LDL and LHP and higher PON1 activities. Additionally, the elevated total cholesterol (TC) and low-density lipoprotein-C (LDL-C) in the L-NAME group were decreased by atorvastatin administration. TC and LDL-C were positively correlated with ox-LDL and LHP and negatively correlated with PON1 in all groups. High-density lipoprotein-C (HDL-C) was negatively correlated with ox-LDL.
  
  
  CONCLUSIONS
  PON1 prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids; its activity showed a pronounced decrease in the L-NAME treatment group and was increased in the atorvastatin group. Based on our findings, we concluded that the atorvastatin had HDL-related antioxidant activity as well as lipid-lowering properties.
authors.affiliation: Department of Biochemistry, Yildiz Technical University , Istanbul.
authors.forename: Volkan
authors.initials: V
authors.lastname: Sozer
authors.forename: Hafize
authors.initials: H
authors.lastname: Uzun
authors.forename: Remise
authors.initials: R
authors.lastname: Gelisgen
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
authors.forename: Rivase
authors.initials: R
authors.lastname: Kalayci
authors.forename: Omur
authors.initials: O
authors.lastname: Tabak
authors.forename: Nadir
authors.initials: N
authors.lastname: Arican
authors.forename: Dildar
authors.initials: D
authors.lastname: Konukoglu
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism; D000069059:Atorvastatin; D004353:Drug Evaluation, Preclinical; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000097:blood
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D013438:Sulfhydryl Compounds; D000069059:Atorvastatin; C572204:Pon1 protein, rat; D043303:Aryldialkylphosphatase; D019331:NG-Nitroarginine Methyl Ester