Fluvastatin normalizes the decreased turnovers of glutathione and ascorbicacid 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 hyper lipidaemic subjects. In order to elucidate one of the mechanisms of this in vivo, we investigated the effects of fluvastatin and pravastatin on the de creased turnovers of reduced glutathione (GSH) and ascorbic acid (AA) in Wa tanabe 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 d ecreased thiobarbituric acid-reactive substances, which were increased in t he plasma of WHHL, 3. Although these drugs did not affect the steady state levels of total glu tathione and low molecular weight thiols in the liver and kidney, fluvastat in markedly normalized the rate of GSH turnover in these tissues, as determ ined by using L-buthionine(S,R)-sulphoximine, a specific inhibitor of GSH s ynthesis. 4. Fluvastatin also increased the clearance of AA from the circulation in W HHL. 5. These results suggest that, in addition to its hypolipidaemic action, fl uvastatin has the potential to improve the turnover of anti-oxidants, which is closely related to the amelioration of the redox status in the body.