[Antagonism of lovastatin on oxidative stress and apoptosis in primary rat hippocampal neurons induced by ß-amyloid peptide].

ABSTRACT

Objective: To investigate the effect of lovastatin on oxidative stress and apoptosis in neurons induced by ß-amyloid peptide (Aß). Methods: Primary culture of rat hippocampal neuron was treated with Aß oligomers alone or combined with lovastatin. The levels of OH(-), H(2)O(2), O(2)·(-), malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were measured by biochemical methods and protein expression of caspase-3 and bcl-2 was detected by Western blot. Results: As compared with the control group, treatment of 0.5 µmol/L Aß oligomers for 48 h led to significant increase of OH(-), H(2)O(2), O(2)·(-) and malondialdehyde content, inhibition of SOD and GSH-PX activities, enhanced caspase-3 expression and decreased bcl-2 expression. Interestingly, these neurotoxic modifications on the levels of OH(-), H(2)O(2), O(2)·(-) and malondialdehyde content, SOD and GSH-PX activities, and the protein expression of cleaved caspase-3 and bcl-2 were significantly attenuated when the cells were pretreated with 0.1 µmol/L lovastatin for 24 h before exposure of Aß oligomers. Conclusion: Lovastatin may play an important role in antagonizing the neurotoxicity of Aß through a mechanism likely related to the inhibition of oxidative stress.