Abstract
This study was undertaken to investigate the impact simvastatin chronotherapy on erythrocytes Nitric Oxide Synthase (NOS) activity. In the present study we select 24 adult human subjects have plasma total cholesterol high borderline (200-230 mg dL(-1)). Subjects were administrated simvastatin (20 mg day time) for 2 months. Afterward, they were recommended for washout period (2 weeks), then subjects were administered the same dose at night time for additional 2 months. The present results showed that both day time and night time simvastatin treatment regimen significantly decrease plasma atherogenic index, malondialdehyde and protein carbonyl levels. However, paraoxonase-1 activity and total thiol level were significantly increased. Moreover, simvastatin therapy improved nitrite (NO marker) levels in both plasma and erythrocytes compared to baselines. As well, simvastatin day time and night time dosing significantly increased erythrocytes NOS activity (46 and 64%, respectively) compared to baselines. Night time dosing induced marked increase of NOS activity (19%) compared to day time. This study confirms that night time dosing boost hypocholesterolemic, antioxidant and NO modulating effects of simvastatin compared to day time.