Doxepin protects cultured neurons against oxidative stress-induced injury.
OBJECTIVE
To investigate protective effects of doxepin (Dox) on cultured neuronal injury induced by oxidative stress.


METHODS
Cytotoxicities of glutamate (Glu 0.5 mmol/L, 15 min), sodium dithionite (0.5 mmol/L, 24 h) or hemoglobin (Hb100 mg/L,24 h)and the protective effects of Dox were observed.


RESULTS
Exposure of cultured neurons to Glu, sodium dithionite and Hb developed a neurotoxicity expressed in the thiazol blue tetrazolium bromide (MTT) assay, the increase of lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) content and intracellular [Ca2+]i accumulation, as well as the decrease of superoxide dismutase (SOD) activity. DOX 1-100 nmol/L significantly inhibited all above changes.


CONCLUSIONS
Dox protects cultured neurons against oxidative stress-induced injury by suppressing intracellular [Ca2+]i accumulation, decreasing lipid peroxide generation and stimulating antioxidant enzyme.
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Bian-sheng
BS
Ji
He
H
Ji
Guo-qing
GQ
Liu
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004227:Dithionite / Q000037:antagonists & inhibitors; D004316:Doxepin / Q000494:pharmacology*; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000633:toxicity; D006454:Hemoglobins / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D006454:Hemoglobins; D018696:Neuroprotective Agents; D004227:Dithionite; D004316:Doxepin; D018698:Glutamic Acid; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D002118:Calcium