Effects of atorvastatin therapy on protein oxidation and oxidative DNA damage in hypercholesterolemic rabbits

被引:45
作者
Aydin, S. [1 ]
Uzun, H. [1 ]
Sozer, V. [2 ]
Altug, T. [3 ]
机构
[1] Istanbul Univ, Cerrahpasa Med Fac, Dept Biochem, TR-34096 Istanbul, Turkey
[2] Yildiz Tech Univ, Dept Biochem, Istanbul, Turkey
[3] Istanbul Univ, Cerrahpasa Med Fac, Expt Anim Res & Breeding Lab, TR-34096 Istanbul, Turkey
关键词
Hypercholesterolemia; Atorvastatin; Protein oxidation; Oxidative DNA damage; Lipid peroxidation; Rat; ATHEROSCLEROSIS; ANTIOXIDANT; COMBINATION; CHOLESTEROL; MANAGEMENT; MODEL;
D O I
10.1016/j.phrs.2009.01.004
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Objective: Our aim was to clarify the effects of hypercholesterolemic diet and administeration of atorvastatin on lipid peroxidation, protein oxidation and oxidative DNA damage in male New Zealand white rabbits. Methods: We determined malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma. Twenty rabbits were randomly divided into two groups and fed with a high-cholesterol diet (fortified with 1% cholesterol) for 4 weeks. Such rabbits were subjected to either (Group 1) a high-cholesterol diet non-supplemented with atorvastatin (n = 10) or (Group 2) a high-cholesterol diet supplemented with atorvastatin (0.3 mg atorvastatin per day/kg body weight) for 4 weeks (n = 10). A control group (n = 5) (Group 3) was fed a cholesterol free diet for 4 weeks. Colorimetric methods were used to determine the level of the oxidative stress markers, except 8-OHdG, which was measured by ELISA. Results: Rabbits were fed with the high-cholesterol diet alone (Group 1) showed higher levels of lipid profile and oxidative protein and DNA damage than compared with dose of the control group (Group 3). Atorvastatin therapy has substantially beneficial effects on oxidative protein and DNA damage in hypercholesterolemic rabbits. Conclusions: The current findings will, we hope, lead to a new insight into the pathogenesis of atherosclerosis. On the other hand inhibition of protein oxidation and DNA oxidation in the plasma by atorvastatin may be one of the pleiotropic effects of statins, and thus the underlying mechanism needs to be further clarifications. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:242 / 247
页数:6
相关论文
共 39 条
[1]
Efficacy of simvastatin and pumpkin-seed oil in the management of dietary-induced hypercholesterolemia [J].
AlZuhair, H ;
AbdElFattah, AA ;
AbdElLatif, HA .
PHARMACOLOGICAL RESEARCH, 1997, 35 (05) :403-408
[2]
*AM PHYS ASS BOARD, GUID ETH COND CAR US
[3]
GLUTATHIONE MONOESTERS [J].
ANDERSON, ME ;
MEISTER, A .
ANALYTICAL BIOCHEMISTRY, 1989, 183 (01) :16-20
[4]
Oxidative stress, DNA damage and vascular endothelial function [J].
Andreassi, M. G. .
BIOMEDICINE & PHARMACOTHERAPY, 2006, 60 (08) :482-482
[5]
Atorvastatin monotherapy vs. combination therapy in the management of patients with combined hyperlipidemia [J].
Avisar, Inbal ;
Brook, J. Gerald ;
Wolfovitz, Efrat .
EUROPEAN JOURNAL OF INTERNAL MEDICINE, 2008, 19 (03) :203-208
[6]
Protein oxidation in aging, disease, and oxidative stress [J].
Berlett, BS ;
Stadtman, ER .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20313-20316
[7]
BEUTLER E, 1963, J LAB CLIN MED, V61, P882
[8]
BLANCOCOLIO LM, 2005, TIMELY TOP MED CARDI, V1, pE16
[9]
Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits - Comparison with lovastatin [J].
Boger, RH ;
BodeBoger, SM ;
Brandes, RP ;
Phivthongngam, L ;
Bohme, M ;
Nafe, R ;
Mugge, A ;
Frolich, JC .
CIRCULATION, 1997, 96 (04) :1282-1290
[10]
High density lipoproteins (HDL) and the oxidative hypothesis of atherosclerosis [J].
Bonnefont-Rousselot, D ;
Thérond, P ;
Beaudeux, JL ;
Peynet, J ;
Legrand, A ;
Delattre, J .
CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 1999, 37 (10) :939-948