Amlodipine besylate and amlodipine camsylate prevent cortical neuronal cell death induced by oxidative stress

Abstract

We examined the neuroprotective effects of the long-acting third-generation dihydropyridine Ca2+ antagonists, amlodipine besylate (AB) and amlodipine camsylate (AC), on neuronal cell death induced by oxidative stress. Cell viability and levels of free radicals and intracellular signaling proteins were measured after treating primary cultures of cortical neurons with AB, AC, and/or hydrogen peroxide (H2O2) under various conditions. Cell viability was not affected by concentrations of AB or AC up to 5 mu M but decreased at higher concentrations. Following H2O2 exposure, the viability of cortical neurons decreased in a concentration-dependent manner; however, treatment with AB or AC up to 5 mu M restored the viability of H2O2-injured cortical neurons. Treatment with H2O2 increased the level of free radicals in cortical neurons, and pre-treatment with AB or AC counteracted this in a dose-dependent manner. Similarly, treatment with AB or AC reduced the declines in p85aPI3K, phosphorylated Akt, phosphorylated GSK-3 beta, heat-shock transcription factor-1, and Bcl-2 induced by H2O2, as well as the increases in cyclooxygenase-2, cytosolic cytochrome c, cleaved caspase 9, and cleaved caspase 3. Our results indicate that AB and AC exert similar neuroprotective effects by reducing oxidative stress, enhancing survival signals, and inhibiting death signals.