Authors: Yan Yang Xiufang Chen Haiyan Min Shiyu Song Juan Zhang Shanshan Fan Long Yi Hongwei Wang Xiaoping Gu Zhengliang Ma Qian Gao
Publish Date: 2016/01/23
Volume: 54, Issue: 2, Pages: 1101-1110
Abstract
Isoflurane exposure induces apoptosis in cultured cells and in the developing brain while the underlying mechanism remains largely unclarified This study was designed to determine whether the disruption of mitoKATPmediated ATP balance was involved in the cytotoxicity of isoflurane Human neuroglioma cells U251 and 7dayold mice were treated with isoflurane A specific mitoKATP antagonist 5HD was used and the cellular ATP levels NAD+/NADH ratios and mitochondrial transmembrane potential ΔΨm were measured Our data showed that the blockage of mitoKATP by 5HD mitigated the isofluraneinduced ΔΨm disruption reactive oxygen species ROS accumulation and apoptosis in U251 cells Moreover we found that the toxic effect of isoflurane was not observed in the first 2h exposure instead the cellular ATP levels and NAD+/NADH ratios were markedly increased The reduction of ATP levels and NAD+/NADH ratios was only detected after this initial phase This dynamical effect of isoflurane was blocked by 5HD In contrast a ROS scavenger NAC sustained the isofluraneinduced ATP elevation Similar results were observed in animal studies And again 5HD attenuated isofluraneinduced cognitive disorders in the Intellicage test a system that assesses place learning behavior in a social environment Our study uncovered a potential mechanism underlying isoflurane’s toxicity with a therapeutic future
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