Hydrogen Sul Fide Antagonizes Formaldrhyde-include Ferroptosis In Hippocampus Of Rats

[Background and Objective]Formaldehyde?FA?is a kind of toxic gas.It's been demonstrated that when the metabolism of formaldehyde is unbalanced in vivo,it usually will cause brain oxidative damage,resulting in neurotoxicity.Hydrogen sulfide?H₂S?,is a kind of endogenous gas molecule,has antioxidant and neuroprotective effects.Ferroptosis is an oxidative cell death,which is closely related to many neurodegenerative diseases.This study aimed to explore whether hydrogen sulfide antagonizes formaldehyde-induced f erroptosis in rat hippocampus and provide a new idea for the prevention and treatment of formaldehyde-induced neurotoxicity.[Methods]1.Expression of glutathione-dependent antioxidant enzyme glutathione peroxidase4?GPX4?in hippocampus tissue was monitored by western blotting.2.The contents of glutathione?GSH?and malondialdehyde?MDA?,4-hydroxynonenal?4-HNE?in hippocampus tissue were detected by e nzyme-linked immunosorbent assay?ELISA?.3.The level of lipid reactive oxygen species?ROS?in hippocampus tissue was evaluated by flow cytometry after C11-BODIPY staining.4.The content of Fe²⁺in hippocampus tissue was evaluated by flow cytometry after calcein-acetoxymethlester Ca-AM staining.5.The average cross section of mitochondrial in the CA3 regions of hippocampus were observed under transmission electron microscopy.[Results]1.Formaldehyde induce ferroptosis in rat hippocampusAfter the rats were treated with 2.5?L of FA?0.1,1,10?M?by unilateral lateral ventricle micro-injection for 7d,Then the hippocampus tissue was taken for detection.1.1 The contents of GSH,MDA and 4-HNE in hippocampus of rats were detected by elisa.The results showed that treatment with FA?0.1,1,10?M?decreased the levels of GSH and increased the contents of MDA and4-HNE in a concentration-dependent manner in hippocampus.1.2 The level of GPX4 in hippocampus was detected by western blotting.The results showed that treatment with FA?0.1,1,10?M?decreased the expression of GPX4 in a concentration-dependent manner in hippocampus.1.3 The contents of ROS and Fe²⁺were detected by C11-BODIPY and Ca-AM staining,The results showed that treatment with FA?10?M?significantly increased the contents of ROS and Fe²⁺in hippocampus.1.4 Transmission electron microscopy showed that FA?1,10?M?significantly decreased the average cross section of mitochondrial in the CA3 regions of hippocampus2.Hydrogen sulfide antagonizes formaldehyde-induced ferroptosis in hippocampus of ratsAfter pretreatment with NaHS?10,30,100?mol/kg/d,i.p.?for 7h,the rats were treated with 2.5?L of FA?1?M,i.c.v.?for 7 d.2.1 The ELISA results showed that NaHS?10,30,100?mol/kg?prevented the reduction of GSH and the increase of MDA and 4-HNE in hippocampus induced by FA at concentration of 1?M.2.2 Western blotting results showed that pretreatment with NaHS?10,30,100?mol/kg?rescued the reduction of GPX4 induced by FA at concentration of 1?M.2.3 The FCM results showed that pretreatment with NaHS?10,30,100?mol/kg?antagonized the increase of ROS and Fe²⁺in hippocampus induced by FA at concentration of 1?M.2.4 Transmission electron microscopy showed that pretreatment with NaHS?30,100?mol/kg?reversed FA-induced decrease average cross section of mitochondrial in the CA3 regions of hippocampus.[Conclusion]1.Hydrogen sulfide prevents formaldehyde-induced ferroptosis in hippocampus of rats...