Dan Chen1,
Yi-Ling Fang1,
Ling-Ling Zhang1,
Xiao-Yin Niu1,
Xiao-Ru Sun1,
Xiao-Zhen Niu1,
Xuan Zhao1,
Cheng Li1 
For correspondence:- Cheng Li Email: chengli0903@163.com Tel:+8613214171828
Accepted: 26 Mar 2020 Published: 30 April 2020
Citation: Chen D, Fang Y, Zhang L, Niu X, Sun X, Niu X, et al. Hydrogen sulfide ameliorates isoflurane-induced cognitive impairment in mice: Implication of caspase-3 activation. Trop J Pharm Res 2020; 19(4):773-780 doi: 10.4314/tjpr.v19i4.14
© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
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.
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