title: Different effects of isoflurane and sevoflurane on cytotoxicity.
abstract: BACKGROUND
  Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum (ER) via activation of inositol 1, 4, 5-trisphosphate (IP(3)) receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species (ROS).
  
  
  METHODS
  Primary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration (MAC) of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca(2+)](c), and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP(3) receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons.
  
  
  RESULTS
  Isoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat cortical neurons, which was also associated with a high and fast elevation of peak [Ca(2+)](c). Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca(2+)](c) in primary rat cortical neurons.
  
  
  CONCLUSIONS
  These results suggested that isoflurane induced elevation in [Ca(2+)](c), partially via elevated activity of IP(3) receptors, which rendered cells vulnerable to isoflurane neurotoxicity. ROS production was not involved in isoflurane-induced neurotoxicity. Sevoflurane, at an equivalent exposure to isoflurane, did not induce similar elevations of [Ca(2+)](c) or neurotoxicity in primary cortical neurons of rat.
authors.affiliation: Department of Anesthesiology, Third Hospital, Hebei Medical University, Shijiazhuang, Hebei 050051, China. wangqiujun8@yahoo.com.cn
authors.forename: Qiu-jun
authors.initials: QJ
authors.lastname: Wang
authors.forename: Ke-zhong
authors.initials: KZ
authors.lastname: Li
authors.forename: Shang-long
authors.initials: SL
authors.lastname: Yao
authors.forename: Zhi-hua
authors.initials: ZH
authors.lastname: Li
authors.forename: Shun-suo
authors.initials: SS
authors.lastname: Liu
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects / Q000502:physiology; D007530:Isoflurane / Q000633:toxicity*; D008738:Methyl Ethers / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008738:Methyl Ethers; D017382:Reactive Oxygen Species; D000077149:Sevoflurane; D007530:Isoflurane; D002118:Calcium