In Vitro Oxidative Stress And Anticholinesterase Effects of Atorvastatin,Simvastatin,And Rosuvastatin in the Mouse Brain

Abstract

Introduction:

Hypolipidemic statins produce adverse neuronal effects, oxidative stress, and alterations of cholinesterase (ChE) activity. This in vitro study examined and ascertained effects of statins (atorvastatin, simvastatin, and rosuvastatin) on mice plasma and whole brain ChE activities and the oxidative stress marker brain malondialdehyde (MDA) level.

Methods:

We used plasma and whole brain samples from male mice. In vitro aqueous concentrations of each of the three statins were at 0 (baseline, control), 10, 25, 50, or 100 μM. The inhibition of plasma and brain ChE activity was determined electrometrically and additionally spectrophotometrically in the brain, together with the determination of brain MDA.

Results:

Statins at 10 to 100 μM in vitro significantly inhibited plasma and brain ChE activity in a concentration-dependent manner. The most effective statin was atorvastatin (41.4% inhibition) at 100 μM. Hydrogen peroxide (500 μM), as a positive control, significantly increased brain MDA level. Statins at in vitro concentrations of 25 to 100 μM significantly increased MDA level in whole brain homogenates. The most effective statin in causing in vitro oxidative stress was rosuvastatin, and the least one was atorvastatin. Spectrophotometric determination of brain ChE activity revealed that statins at 25 to 100 μM significantly inhibited the enzyme activity. Hydrogen peroxide (500 μM) also decreased brain ChE activity.

Conclusion:

The in vitro anti-ChE and oxidative stress effects of statins support their adverse/pleiotropic actions in vivo. Other statins should be screened for such effects as they differ considerably in their pharmacologic properties.