Fluvastatin depresses the enhanced lipid peroxidation in vitamin E-deficient hamsters.
Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has recently been reported to have the antioxidative activity in vitro. However, it is still unclear whether chronic treatment with this drug actually leads to amelioration of the redox status in the body. In this study, we investigated the antioxidative effect of fluvastatin in vivo, using a vitamin E-deficient hamster model, an in vivo model of enhanced oxidative stress. After pre-treatment with a vitamin E-deficient diet for 2 months, fluvastatin, pravastatin or probucol was added to the diet for 1 month. Vitamin E deficiency caused a significant increase in the levels of plasma oxidative stress markers such as 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and hydroperoxides. Furthermore, there was a significant increase in the oxidizability of plasma lipids in the vitamin E-deficient animals, indicating that the oxidative stress was increased in the circulation. Fluvastatin markedly depressed the above oxidative stress markers in plasma, and significantly decreased the oxidizability of plasma lipids without affecting their levels. Probucol, a reference antioxidant, also showed a similar effect while pravastatin, another HMG-CoA reductase inhibitor, showed only a weak improvement. We suggest that the treatment with fluvastatin leads to a reduction of oxidative stress in vivo, which is mainly derived from its antioxidative property rather than its lipid-lowering activity.
Suzumura
K
K
Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd, Toda, Saitama, Japan. suzumura@tanabe.co.jp
Ohashi
N
N
Oka
K
K
Yasuhara
M
M
Narita
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D015237:Dinoprost / Q000031:analogs & derivatives*; D004435:Eating / Q000187:drug effects; D028441:F2-Isoprostanes / Q000097:blood / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology*; D000077340:Fluvastatin; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000097:blood; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013997:Time Factors; D014810:Vitamin E / Q000097:blood / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000097:blood / Q000378:metabolism*
D028441:F2-Isoprostanes; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008054:Lipid Peroxides; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D000077340:Fluvastatin; D015237:Dinoprost