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Amlodipine besylate and amlodipine camsylate prevent cortical neuronal cell death induced by oxidative stress
Author(s) -
Lee Young Joo,
Park HyunHee,
Koh SeongHo,
Choi NaYoung,
Lee KyuYong
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07529.x
Subject(s) - neuroprotection , viability assay , oxidative stress , programmed cell death , chemistry , amlodipine , pharmacology , apoptosis , cytosol , intracellular , cytochrome c , microbiology and biotechnology , biochemistry , biology , endocrinology , enzyme , blood pressure
J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07529.x Abstract We examined the neuroprotective effects of the long‐acting third‐generation dihydropyridine Ca 2+ 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 (H 2 O 2 ) under various conditions. Cell viability was not affected by concentrations of AB or AC up to 5 μM but decreased at higher concentrations. Following H 2 O 2 exposure, the viability of cortical neurons decreased in a concentration‐dependent manner; however, treatment with AB or AC up to 5 μM restored the viability of H 2 O 2 ‐injured cortical neurons. Treatment with H 2 O 2 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 p85 a PI3K, phosphorylated Akt, phosphorylated GSK‐3β, heat‐shock transcription factor‐1, and Bcl‐2 induced by H 2 O 2 , 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.