Abstract
The inhalation anesthetic isoflurane has been reported to induce caspase activation and apoptosis, which may lead to learning and memory impairment. However, the underlying mechanisms of these effects are largely unknown. Isoflurane has been shown to induce elevation of cytosol calcium levels, accumulation of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore, reduction in mitochondria membrane potential, and release of cytochrome c. The time course of these effects, however, remains to be determined. Therefore, we performed a pilot study to determine the effects of treatment with isoflurane for various times on ROS levels in HEK-293 cells. The cells were treated with 2% isoflurane plus 21% O2 and 5% CO2 for 15, 30, 60, or 90 min. We then used fluorescence imaging and microplate fluorometer to detect ROS levels. We show that 2% isoflurane for 60 or 90 min, but not 15 or 30 min, induced ROS accumulation in the cells. These data illustrated that isoflurane could cause time-dependent effects on ROS levels. These findings have established a system to further determine the time course effects of isoflurane on cellular and mitochondria function. Ultimately, the studies would elucidate, at least partially, the underlying mechanisms of isoflurane-induced cellular toxicity.
Highlights
It has been reported that children who have multiple exposures to anesthesia and surgery at an early age may develop deficiency of cognitive function ([1,2], reviewed in [3])
HEK-293 cells to further assess the effects of isoflurane on reactive oxygen species (ROS) levels and other mitochondrial function, and to elucidate the underlying mechanisms in the future studies
Our previous studies have shown that treatment with 2% isoflurane for 6 h can induce ROS
Summary
It has been reported that children who have multiple exposures (e.g., three times) to anesthesia and surgery at an early age (e.g., before age 4) may develop deficiency of cognitive function ([1,2], reviewed in [3]). Isoflurane has been shown to induce caspase-3 activation and potentiate the nociceptive stimulation-induced cognitive impairment [16]. The up-stream mechanism by which isoflurane induces caspase activation and apoptosis remains largely to be determined. ROS is generated when the voltage gradient is high because of increased flux of electron donors. Whether the ROS generation is time dependent remains largely to be determined. Our previous studies have shown that isoflurane can induce ROS accumulation, which may cause caspase-3 activation [25,26]. In the present study, we set out to determine the effects of the treatment with 2% isoflurane for different periods of time (e.g., 15, 30, 60, and 90 min) on ROS levels in cultured cells. The hypothesis in the current study is that the isoflurane-induced ROS accumulation is time dependent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
