Ebselen induced C6 glioma cell death in oxygen and glucose deprivation.
Studies have shown that ebselen is an antiinflammatory and antioxidative agent. Its protective effect has been investigated in oxidative stress related diseases such as cerebral ischemia in recent years. However, experimental evidence also shows that ebselen causes cell death in several different cell types. Whether ebselen will have a beneficial or detrimental effect on cells under ischemic condition is not known. Herein, we studied the effect of ebselen on C6 glioma cells under oxygen and glucose deprivation (OGD), an in vitro ischemic model. We found that ebselen significantly enhanced cell death after 3 h of OGD as observed by lactase dehydrogenase (LDH) release and cellular morphological changes. Further studies revealed that depletion of cellular glutathione level by the combined action of ebselen and OGD played a role in enhanced cell death as demonstrated by the following evidence: (1) cellular GSH was significantly depleted by the combined effort of ebselen and OGD, compared to that of ebselen or OGD insult alone; (2) exogenous addition of N-acetyl cysteine completely diminished the cell damage induced by ebselen and OGD; (3) supplement of glucose, which provides cellular reducing agents and thus maintains cellular GSH level, to the OGD medium diminished C6 cell damage induced by ebselen. We conclude that depleting cellular glutathione plays an important role in ebselen-induced cell death with OGD. Our results suggest that ebselen can have a beneficial or toxic effect, depending on the availability of GSH.
Shi
Honglian
H
Pharmaceutical Sciences Division, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA. hshi@salud.umn.edu
Liu
Shimin
S
Miyake
Minoru
M
Liu
Ke Jian
KJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000975:Antioxidants / Q000633:toxicity; D001393:Azoles / Q000633:toxicity*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma; D005947:Glucose / Q000172:deficiency; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005947:Glucose