Amlodipine and glutathione cycle in hypercholesterolaemia.
OBJECTIVE
Effects of amlodipine on lipid peroxidation and alterations in glutathione and related enzymes in blood and aortic tissue were investigated in a cholesterol-induced atherosclerotic rabbit model.


RESULTS
New Zealand white male rabbits were fed with regular chow (group I), chow supplemented with I% cholesterol (group II), regular chow plus amlodipine 5 mg/kg/day p.o. (group III) and I% cholesterol diet supplemented with amlodipine (group IV) for 8 weeks. Cholesterol, malondialdehyde (MDA), reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GSH-PX) and glutathione reductase (GSH-Rd) were determined in blood samples drawn before and after the experimental period. Aortic tissue was examined morphologically for atherosclerotic changes and tissue cholesterol, MDA, GSSG, GSH-PX, GSH-Rd and glutathione-S-transferase (GST) were measured. After 8 weeks, blood cholesterol, MDA, GSSG and GSH-PX were elevated in groups II and IV; GSH was reduced in group IV; MDA levels were higher in group II than in group IV. Aortic tissue investigations revealed higher cholesterol and MDA concentrations in group II than in group IV. Morphological examination of aortic tissues exhibited endothelial disarrangement and lipid deposition in group II. Histopathological alterations related to atherogenesis were less in group IV than in group II.


CONCLUSIONS
Amlodipine reduced the increase in oxidative stress by inhibiting excessive MDA production. Accelerated glutathione redox cycle activity of erythrocytes from animals supplemented with amlodipine suggests that this drug may reduce oxidative stress by enhancing the glutathione system. However, this drug does not seem to affect the glutathione redox cycle in the aortic tissue.
Mutaf
Işil
I
Department of Clinical Biochemistry, Ege University School of Medicine, 35100 Bornova, Izmir, Turkey.
Habif
Sara
S
Turgan
Nevbahar
N
Parildar
Zuhal
Z
Ozmen
Dilek
D
Bayindir
Oya
O
Uysal
Ayşegül
A
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary; D005978:Glutathione / Q000187:drug effects*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits
D002791:Cholesterol, Dietary; D017311:Amlodipine; D008315:Malondialdehyde; D002784:Cholesterol; D005978:Glutathione