Deferoxamine Mesylate Improves Formaldehyde-induced Cognitive Impairment By Inhibiting Ferroptosis Of Hippocampal Nerve Cells

[Background]Formaldehyde（FA）is a common environmental pollutant.Long-term exposure to formaldehyde in the environment and accumulation of endogenous formaldehyde can cause neurotoxicity and induce cognitive impairment.Ferroptosis is an iron-dependent form of cell death,which is closely related to a variety of cognitive impairment diseases.Deferoxamine（DFO）is a kind of iron chelating agent that can combine with excess iron.According to related studies,deferoxamine may play a neuroprotective effect by reducing the accumulation of iron ions in the body.This study will explore whether deferoxamine’s antagonism of formaldehyde-induced cognitive impairment is related to the inhibition of hippocampal iron death in rats.[Objective]To explore the therapeutic effect and mechanism of deferoxamine mesylate on formaldehyde-induced cognitive impairment[Methods]120 male rats were randomly divided into 8 groups,control、FA、FA+0.5μg DFO、FA+2.5μg DF0、FA+5μg DFO、0.5μg DFO、2.5μg DFO、5μg DFO,FA and/or DFO were administered in groups in the lateral ventricle,and two weeks after the administration,two cognitive-behavioral experiments,new object recognition and water maze,were performed to examine the learning memory and cognitive function of the rats,while the rats were anesthetized and executed,and the morphology and size of mitochondria in the CA3 region of the hippocampus were removed and observed by transmission electron microscopy.The levels of lipid reactive oxygen species（ROS）and Fe²⁺in the rat hippocampus were measured by ROS kit,Western Blot detects the expression of Glutathione peroxidase 4（GPX4）and Acyl-Co A synthetase long-chain family member 4（ACSL4）in rat hippocampus Level,MDA,4-HNE kit TBA content of rat hippocampus primary method of peroxidation product MDA and 4-hydroxy-nonanoic acidwere detected.[Results]Rats were injected with FA（1μmol）,2μl/day through the lateral ventricle for 6 hours,and then injected with DFO（0.5,2.5,5μg）,2μl/day,through the lateral ventricle.After 14 days of continuous administration,the following tests were performed:（1）Water maze test results It is shown that DFO（0.5,2.5,5μg）significantly shortens the latency of the FA-induced rats seeking platform swimming route and positioning navigation experiment,and improves the decrease of the swimming time ratio in the middle ring in the space search experiment,suggesting that DFO has an effect on formaldehyde.The induced impairment of cognitive function in rats has an improving effect;（2）The results of novel object recognition experiments show that DFO（2.5,5μg）significantly improves the decrease in the novel object recognition index of rats caused by FA,and（3）transmission Electron microscopy results show that DFO（5μg）can significantly improve the atrophy of hippocampal mitochondria,suggesting that DFO can antagonize FA to promote hippocampal iron death in rats;（4）DCFH-DA fluorescent probe detects the ROS content of rat hippocampus.The results show that compared with the control group,the ROS content of FA is significantly increased.DFO（0.5,2.5,5μg）can inhibit FA-induced ROS content Increase;（5）Tissue iron kit colorimetric method detects Fe²⁺content.Compared with the control group,the Fe²⁺content of the FA treatment group is significantly higher.Compared with the FA treatment group alone,DFO（2.5,5μg）can make Fe²⁺content of rats in the treatment group was significantly reduced,but there was no significant difference between DFO alone and the control group.（6）Western Blot test results showed that DFO（0.5,2.5,5μg）can antagonize the FA-induced reduction of GPX4 expression in hippocampus and the increase of ACSL4 expression level.（7）The results of MDA,4-HNE kit TBA showed that DFO（5μg）can antagonize the FA-induced increase in the content of MDA and 4-HNE in the hippocampus,suggesting that DFO（5μg）can reduce FA by enhancing the antioxidant capacity of rats Damage to the cognitive function of rats.[Conclusion]Deferoxamine mesylate can alleviate formaldehyde-induced cognitive impairment,and its mechanism may involve inhibiting iron death of hippocampal nerve cells in rats.