Hydrogen sulfide ameliorates isoflurane-induced cognitive impairment in mice: Implication of caspase-3 activation

  • Dan Chen
  • Yi-Ling Fang
  • Ling-Ling Zhang
  • Xiao-Yin Niu
  • Xiao-Ru Sun
  • Xiao-Zhen Niu
  • Xuan Zhao
  • Cheng Li
Keywords: Hydrogen sulfide, isoflurane-cognition,fear conditioning,neurotoxicity

Abstract

Purpose: Isoflurane could induce cognitive impairment and activate caspase-3. However, the mechanism of action is unclear and target  interventions are unavailable. The present study examined the potential protective function of hydrogen sulfide (H2S) against isoflurane-induced cognitive impairment.
Methods: Effects of NaHS (5 mg/kg) on cognitive impairment induced by isoflurane (1.4% for 2 h) were assessed using a fear-conditioning test in a group of 8-month old mice. H4 human neuroglioma cells, which were transfected with upregulated human amyloid precursor protein were treated for 3 or 6 h with 2% isoflurane, in the presence of 100-μM NaHS in the mice. A group of mice treated with normal saline in place of the NaHS in each case served as control. Western blotting, fluorescence assay, and a mitochondrial swelling assay were employed to observe the results of caspase-3 activation, mitochondrial dysfunction, and ROS and ATP levels.
Results: NaHS significantly mitigated isoflurane-induced cognitive impairment in mice. In cultured cells, NaHS reduced caspase-3 activation, ROS, mitochondria membrane reduction, mitochondrial permeability transition pore opening, and cellular ATP level. NaHS could ameliorate cognitive
impariment induced by isoflurane through inhibiting caspase-3 activation, oxidative stress, and mitochondrial dysfunction.
Conclusion: These results indicate that hydrogen sulfide (H2S) has potential protective function against isoflurane-induced cognitive impairment. Further investigation of NaHS as an intervention to attenuate anesthesia-associated neurotoxicity is vital.

Keywords: Hydrogen sulfide, isoflurane-cognition,fear conditioning,neurotoxicity

Published
2020-05-14
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996