Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E.
OBJECTIVE
Statins inhibit oxidative stress, but the interplay between cholesterol lowering and antioxidant vitamins is still unclear. Aims of the study were to assess if statins inhibit oxidative stress independently from cholesterol lowering, to assess the behaviour of vitamin E simultaneously with the changes of oxidative stress, to determine in vitro if atorvastatin was able to directly influence platelet-mediated LDL oxidation and vitamin E consumption.


RESULTS
In 30 hypercholesterolaemic patients (HC) and 20 healthy subjects (HS), urinary isoprostanes and plasma vitamin E were determined. The HC were randomized to diet or diet plus atorvastatin 10 mg/day. Compared with HS, HC had higher isoprostanes and lower vitamin E levels. The statin-allocated group showed a reduction of isoprostanes after only 3 days (-18.8%, P < 0.01); after 30 days, a stronger reduction of isoprostanes was noted (-37.1%, P < 0.01) whereas an increase of vitamin E (+42%, P < 0.01) and a reduction of cholesterol (-24.9%, P < 0.01) were observed. The diet-allocated group showed a weak decrease of cholesterol after 30 days. In vitro study showed that atorvastatin dose-dependently inhibited platelet-mediated LDL oxidation and isoprostane formation with a mechanism involving NADPH-oxidase.


CONCLUSIONS
The study provides the first evidence that atorvastatin exerts an early antioxidant effect that could contribute to enhancing circulating vitamin E.
IV Divisione di Clinica Medica, Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Viale del Policlinico 155, Rome 00161, Italy.
Roberto
R
Cangemi
Lorenzo
L
Loffredo
Roberto
R
Carnevale
Ludovica
L
Perri
Maria Patrizia
MP
Patrizi
Valerio
V
Sanguigni
Pasquale
P
Pignatelli
Francesco
F
Violi
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D008078:Cholesterol, LDL / Q000187:drug effects / Q000494:pharmacology; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy*; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use*; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000097:blood*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D028421:Isoprostanes; D011758:Pyrroles; D013481:Superoxides; D014810:Vitamin E; D000069059:Atorvastatin; D019255:NADPH Oxidases