Open AccessDiphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
Author(s) -
Qin Fu,
Naiyong Gao,
Fengyuan Che,
GuangYin Xu,
Hongxing Han,
Qiang Su,
Genshan Ma
Publication year - 2019
Publication title -
journal of integrative neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.336
H-Index - 33
eISSN - 1757-448X
pISSN - 0219-6352
DOI - 10.31083/j.jin.2019.04.1174
Subject(s) - nicotinamide adenine dinucleotide phosphate , neurotoxicity , chemistry , diazoxide , reactive oxygen species , nadph oxidase , viability assay , biochemistry , pharmacology , apoptosis , oxidase test , endocrinology , toxicity , biology , enzyme , organic chemistry , insulin
We examined synergistic effects of inhibiting reactive oxygen species generated from the mitochondria and from nicotinamide adenine dinucleotide phosphate oxidase on neurotoxicity. Primary hippocampal neurons were exposed to amyloid β, and the cells were treated with diazoxide or/and diphenyleneiodonium chloride. We found that the cell viability was decreased significantly after exposure to amyloid β for 72 h with higer reactive oxygen species and malondialdehyde levels, higher caspase-3 and cleaved caspase-3 levels and lower B-cell lymphoma 2 (Bcl-2) level. Both diazoxide and diphenyleneiodonium increased cell viability by inhibiting the increase in reactive oxygen species and caspase-3 activity as well as the decrease in Bcl-2 induced by amyloid β. The combination of diazoxide and diphenyleneiodonium exhibited better protective effects compared to a single treatment. In conclusion, the activation of a mitochondrial potassium channel in combination with the inhibitor of nicotinamide adenine dinucleotide phosphate oxidase exhibit synergistic protective effects against amyloid β neurotoxicity.