Fluvastatin protects neuronal cells from hydrogen peroxide-induced toxicity with decreasing oxidative damage and...

Statins, the most effective lipoprotein-cholesterol lowering drugs, are widely used for patients with cardiovascular disease. The pleiotropic effects of statins have been recently gained attention for their both beneficial and deleterious effects on neurons. We investigated the effects and molecular mechanisms of fluvastatin at clinically relevant concentrations on neuronal cells after induction of oxidative stress.

Both SH-SY5Y, a representative cell line for in vitro neurone model, and human primary neuronal cells were applied. Cellular and biochemical assays were used to investigate the effects of fluvastatin in neurone cells.

Fluvastatin significantly restored H2O2-induced neuronal death in a dose-dependent manner (P < 0.05) and reversed H2O2-induced oxidative stress and damage via restoring mitochondrial function in neuronal cells (P < 0.05). Although fluvastatin inhibited prenylation in neuronal cells, the protective effects of fluvastatin against H2O2-induced neuronal cytotoxicity are not associated with prenylation inhibition or AMPK activation. In contrast, PI3K/Akt/mTOR activation mediated fluvastatin's neuroprotective activity (P < 0.05).

Our work demonstrates the beneficial effects of fluvastatin in neuronal cells under pathological conditions, and, furthermore, this is via prenylation-independent activation of PI3K/Akt/mTOR pathway. Our data highlights the functional significance of the PI3K/Akt/mTOR pathway in neuronal cells in response to oxidative stress.