Fluvastatin normalizes the decreased turnovers of glutathione and ascorbic acid in Watanabe heritable hyperlipidaemic rabbits.
1. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to decrease the oxidizability of plasma lipids in hyperlipidaemic subjects. In order to elucidate one of the mechanisms of this in vivo, we investigated the effects of fluvastatin and pravastatin on the decreased turnovers of reduced glutathione (GSH) and ascorbic acid (AA) in Watanabe heritable hyperlipidaemic (WHHL) rabbits. 2. These drugs (30 mg/kg per day) equally decreased plasma levels of lipids after a 4 week treatment period. However, only fluvastatin significantly decreased thiobarbituric acid-reactive substances, which were increased in the plasma of WHHL. 3. Although these drugs did not affect the steady state levels of total glutathione and low molecular weight thiols in the liver and kidney, fluvastatin markedly normalized the rate of GSH turnover in these tissues, as determined by using L-buthionine-(S,R)-sulphoximine, a specific inhibitor of GSH synthesis. 4. Fluvastatin also increased the clearance of AA from the circulation in WHHL. 5. These results suggest that, in addition to its hypolipidaemic action, fluvastatin has the potential to improve the turnover of anti-oxidants, which is closely related to the amelioration of the redox status in the body.
Suzumura
K
K
Department of Biochemistry, Osaka City University Medical School, Osaka, Japan. suzumura@tanabe.co.jp
Kasahara
E
E
Ohnishi
Y
Y
Chien
K C
KC
Inoue
M
M
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology; D001205:Ascorbic Acid / Q000097:blood / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin / Q000494:pharmacology; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D000963:Antimetabolites; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010743:Phospholipids; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D000077340:Fluvastatin; D019328:Buthionine Sulfoximine; D002784:Cholesterol; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione; D017035:Pravastatin; D001205:Ascorbic Acid