Protective effect of endothelin antagonist (TAK-044) on neuronal cell viability in in vitro oxygen-glucose deprivation model of stroke.
The present study was carried to investigate the effect of endothelin antagonist (TAK-044) in an in vitro model of stroke using primary neuronal culture. Hypoxia in neuronal culture was induced for 3 h using oxygen glucose deprivation (OGD) model, thereafter cells were reperfused. In separate group cultures were incubated with graded concentrations of TAK-044 (0.01, 0.1 and 1 microg/microl) for different time duration i.e. 6, 12 and 24 hours after reperfusion. Percent cell viability was assessed 24 h after reperfusion using MTT assay. It was observed that percent cell viability was reduced to 13.7 +/- 0.4% in the cells under 3 h hypoxic condition as compared to the cells under normal condition (100%). TAK-044 at the concentrations of 0.1 and 1 microg/microl, but not at 0.01 microg/microl showed significant (P<0.01) improvement in the % cell viability as compared to the cells in hypoxic condition. Percent cell viability at the concentration of 0.1 and 1 microg/microl for 24 h time duration after reperfusion were 54.8 +/- 3.2% and 75.4 +/- 1.8% respectively as compared to the cells under hypoxic condition (13.7 +/- 0.4%). The results demonstrate the neuroprotective effect of TAK-044 against neuronal damage caused by hypoxia induced in neuronal culture.
Briyal
Seema
S
Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 575 001.
Pant
Aditya B
AB
Gupta
Y K
YK
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D020521:Stroke / Q000188:drug therapy*
D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; C088196:TAK 044; D005947:Glucose