Doxepin protects cultured neurons against oxidative stress-induced injury

Acta Pharmacol Sin. 2004 Mar;25(3):297-300.

Abstract

Aim: 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.

Conclusion: Dox protects cultured neurons against oxidative stress-induced injury by suppressing intracellular [Ca2+]i accumulation, decreasing lipid peroxide generation and stimulating antioxidant enzyme.

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology
  • Calcium / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism*
  • Dithionite / antagonists & inhibitors
  • Doxepin / pharmacology*
  • Embryo, Mammalian
  • Glutamic Acid / toxicity
  • Hemoglobins / antagonists & inhibitors
  • L-Lactate Dehydrogenase / metabolism
  • Malondialdehyde / metabolism
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress*
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Antidepressive Agents, Tricyclic
  • Hemoglobins
  • Neuroprotective Agents
  • Dithionite
  • Doxepin
  • Glutamic Acid
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Superoxide Dismutase
  • Calcium