Physicochemical modifications induced by statins therapy on human erythrocytes membranes.
In hyperlipidemia damage to the plasma membranes of erythrocytes is observed. It is supposed that statins by their beneficial impact on the serum lipids and pleiotropic effects may modify the membrane cell structure.


METHODS
The aim of the study was to evaluate the effects of statins on erythrocyte membrane structure in patients (pts) with hyperlipidemia. The study involved 54 pts with the initial total cholesterol (TC) concentration > 200 mg/dl (6.5 mmol/l), low-density lipoprotein cholesterol (LDL-C) > 160 mg/dl (4.1 mmol/l) and triglycerides (TG) < 400 mg/dl (4.5 mmol/l) and 22 healthy individuals as the control group. After 8 weeks of hypolipemic diet, pts were randomized to two groups: A--27 pts treated with atorvastatin in a dose of 10 mg/day; S--27 pts treated with simvastatin in a dose of 40 mg/day. After 8 weeks of active therapy in all pts were determined: the activity of Na+K+-ATPase, erythrocyte membrane fluidity (the order parameter S), lipids peroxidation (thiobarbituric acid-reactive substances - TBARS), content of membrane cholesterol, concentration of SH groups and W/S ratio (which specifies the relations between the two kinds of the SH groups: the weakly--W bound, and the strongly--S bound).


RESULTS
In the group of hyperlipidemic patients as compared to the control group we observed significantly higher values of the order parameter S, membrane cholesterol, TBARS, ratio W/S and significantly lower the activity of Na+K+-ATPase, SH groups concentration in membrane erythrocytes. Atorvastatin and simvastatin in a similar degree significantly increased the activity of Na'K'-ATPase (15.7% vs. 20.9%), the SH concentration groups (23.4% vs. 21.2%) and decreased TBARS (-41.8% vs. -41%), W/S ratio (-11.3% vs. S-12.1%). Simvastatin decreased stronger the membrane cholesterol (-30.0% vs. -24.5%; p < 0.05) and the values of parameter S (-5.1% vs. -3.5%, p < 0.05) than atorvastatin.


CONCLUSIONS
A short-term therapy with statins exhibits a high hypolipemic efficacy and advantageous effects on the protein-lipid structure of erythrocyte membranes. Simvastatin at 40 mg/day dose increases the fluidity of erythrocyte membrane and decreases the membrane cholesterol level to a greater extent than does atorvastatin at 10 mg/day dose.
Broncel
Marlena
M
Department of Internal Diseases with Clinical Pharmacology and Therapy Monitoring Unit, University of Lodz, Poland. ttm@ttm.org.pl
Bała
Agnieszka
A
Koter-Michalak
Maria
M
Duchnowicz
Piotr
P
Wojsznis
Waldemar
W
Chojnowska-Jezierska
Julita
J
D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008563:Membrane Lipids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin; D019821:Simvastatin; D000254:Sodium-Potassium-Exchanging ATPase