Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders....Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders.Mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.Currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.展开更多
This study aimed to analyze the effect of lipid peroxidation on the allergenicity and functional properties of soybeanβ-conglycinin(7 S)and glycinin(11 S).Oxidation complexes were determined using the lipid peroxidat...This study aimed to analyze the effect of lipid peroxidation on the allergenicity and functional properties of soybeanβ-conglycinin(7 S)and glycinin(11 S).Oxidation complexes were determined using the lipid peroxidation method.Functional properties were analyzed based on emulsifying and foaming properties.The potential allergenicity was evaluated by in vitro and in vivo methods.The results found that oxidation altered structures of the proteins and resulted in the formation of cross-linked protein polymers.The emulsion and foaming properties of the proteins were improved after oxidation.The IgE-binding capacity of 7 S and11 S reduced after oxidation.KU812 cell assays showed that both histamine and IL-4 release decreased after oxidation treatment.A mouse model showed that oxidation reduced the IgE,IgG,and IgG1 levels,as well as reduced histamine and mMCP-1 release in serum,which might suppress the allergic reaction.In conclusion,the lipid peroxidation treatment likely causes changes to the functional properties of soybean,decreasing the potential allergenicity of 7 S and 11 S.展开更多
Heavy metals have harmful effects on human health,and exposure to these metals has been increased by industrial and anthropogenic activities and modern industrialization.Heavy metals content of the liver tissues was d...Heavy metals have harmful effects on human health,and exposure to these metals has been increased by industrial and anthropogenic activities and modern industrialization.Heavy metals content of the liver tissues was determine d using Atomic Absorption Spectrophotometer method,while lipid peroxidation was carried out.Heavy metals analyzed include;lead(Pb),cadmium(Cd),zinc(Zn),Arsenic(As),and Mercury(Hg).The findings revealed that the heavy metal Zinc(Zn)has high concentrations in the muscles of the fish species,the concentration of this heavy metal Zinc is high in River Gindin Dorowa th a n in River Ibi and River Donga shows less concentration of this heavy metal though it’s above WHO permissible limits.Results revealed that only Zn and Cd were present in the muscle from the three rivers.Pb was found only in the liver from Gindin-Dorowa at the concentration of 0.017 mg/kg,which is not significant(P<0.05)when compared with other locations,while Hg and As were absent in all the muscle samples.The highest concentration of Zn was found in the muscle sample from Gindin-Dorowa(7.450 mg/kg)followed by Ibi(6.16 mg/kg)and the least being Donga(4.365 mg/kg)which are significantly(P<0.05)different from one another.However,there was no significant(P<0.05)difference among the Cd composition of muscle from Gindin-Dorowa(0.025 mg/kg),Donga(0.024 mg/kg)and Ibi(0.015 mg/kg),respectively.The TBA was found in the hepatic tissue sample from Gidin-Dorowa,which has the highest Zn,Cd and no Pb content,followed by Ibi and then the Donga sample.This suggests that there is a positive relationship between heavy metals and the effect of TBA on the hepatic tissues,justifying the fact that heavy metals affect the hepatic tissues of fish,while on the cerebral tissue.In conclusion,it revealed that there is a negative relation between heavy metals and the effect of TBA on the cerebral tissues to protect or save aquatic habitat s of fish quality and aquatic life.展开更多
Dietary omega-3 (n - 3) polyunsaturated fatty acids (PUFA) are recommended by public health organizations to reduce the risk of cardiovascular disease, and several epidemiological studies have suggested there is an in...Dietary omega-3 (n - 3) polyunsaturated fatty acids (PUFA) are recommended by public health organizations to reduce the risk of cardiovascular disease, and several epidemiological studies have suggested there is an inverse association between n - 3 intake and human cancers. However, n - 3 are susceptible to an increase in lipid peroxidation in the human body. As part of a crossover dietary intervention study of a diet (20% of energy from fat) with or without an additional 3% of energy from a mixture of n - 3 (with 5.36 g α-linolenic acid and 1.45 g eicosapentaenoic acid and docosahexaenoic acid per 2000 kcal per day), we measured total in vivo lipid peroxidation in healthy postmenopausal women (n = 15). Our results indicated that the diet with 3% of energy from n - 3 significantly increased the urinary concentrations of total polar lipophilic aldehydes and related compounds produced via lipid peroxidation (p α, β-unsaturated hydroxy aldehydes 4-hydroxy-2-trans - hexenal (p trans -decenal (p < 0.05) compared to the diet with less than 1% of energy from n - 3. This is also the first study to document the presence of 4-hydroxy-2-trans -decenal in the urine of individuals consuming n - 3. These results demonstrate that an increase in 3% of energy from dietary n – 3 increases in vivo lipid peroxidation.展开更多
Lipoxidation is formed during the oxidation of lipids and specific proteins,causing an alteration in proteins function.Although this occurs under physiological conditions,in many cases,it has been associated with path...Lipoxidation is formed during the oxidation of lipids and specific proteins,causing an alteration in proteins function.Although this occurs under physiological conditions,in many cases,it has been associated with pathological processes,including cancer.Oxidative DNA damage is a significant contributor to cancer development,and lipoxidation products such as malondialdehyde(MDA)and 4-hydroxy-2-nonenal(4-HNE)play a role in the induction of mutations responsible for DNA modifications.Elevations of reactive aldehydes can be seen in patients with metastatic disease in comparison to those without metastatic disease.Lipoxidation adducts can modify the immune response,consequently causing either positive or negative alterations in cancer progression.When reactive aldehydes are added to tumor cells,they exert similar effects to chemotherapeutic drugs by forming DNA adducts and consequently steer the tumor cells toward apoptosis.This article highlights the role of botanical compounds in lipid metabolism,lipid peroxidation,and cell cycle arrest and discusses the potential role they may have in oncology treatments.展开更多
The joint toxicity of Penta-BDE(Pe-BDE)and heavy metals including cadmium and copper on Daphnia magna(D.magna)was evaluated on the basis of determining the 48 h survival,antioxidative enzyme responses,and lipid peroxi...The joint toxicity of Penta-BDE(Pe-BDE)and heavy metals including cadmium and copper on Daphnia magna(D.magna)was evaluated on the basis of determining the 48 h survival,antioxidative enzyme responses,and lipid peroxidation.The response was classified as additive,greater than additive,or less than additive by comparing the measured“toxic units,TU”with one.Based on the survival of D.magna,less-than-additive interactions were found in most of mixtures treatments.This may be attributed to the different toxicity mechanism between Pe-BDE and metals.Cu and Cd played a greater role in toxicity than what Pe-BDE did.As for the superoxide dismutase(SOD)and catalase(CAT)activity,most response was less than additive.For the glutathione S-transferases(GST)activity,most of the greater-thanadditive responses were found in the Cu plus Pe-BDE treatments,but the additive responses occurred in Cd plus Pe-BDE treatments and binary metal treatments.For lipid peroxide levels,which were measured as malondialdehyde(MDA)levels,less-than-additive response occurred in the 50%Cd plus 50%Cu and ternary mixture treatments.Results suggested that Pe-BDE,Cd,and Cu could induce different patterns of antioxidant enzyme responses,such as antioxidant/prooxidant responses,depending on their capability to produce reactive oxygen species and antioxidant enzymes to detoxify them.展开更多
The germination of laser-irradiated Chinese pine seeds was carried out under drought stress.The activities of superoxide dismutase(SOD)and peroxidase(POD),and the content of malondialdehyde(MDA)were determined.Results...The germination of laser-irradiated Chinese pine seeds was carried out under drought stress.The activities of superoxide dismutase(SOD)and peroxidase(POD),and the content of malondialdehyde(MDA)were determined.Results showed notably increased germination percentage,root length,vitality index and fresh weight.The SOD and POD protective enzyme system activity of the Chinese pine seedlings obviously rose.It can be concluded that the germi-nation and juvenile resistance of Chinese pine seeds under drought stress are enhanced after laser processing.展开更多
Ferroptosis is a cell death pathway mediated by iron-dependent accumulation of lipid peroxide.However,the specific downstream molecular events of iron-dependent lipid peroxidation are yet to be elucidated.In this stud...Ferroptosis is a cell death pathway mediated by iron-dependent accumulation of lipid peroxide.However,the specific downstream molecular events of iron-dependent lipid peroxidation are yet to be elucidated.In this study,based on various spectral analyses,we have found evidence that singlet oxygen is produced through the Russell mechanism during the self-reaction of lipid peroxyl radicals generated via iron-dependent lipid peroxidation regardless of the presence of cholesterol.Significantly reduced generation of singlet oxygen was observed in the absence of iron.The generated singlet oxygen accelerated the oxidative damage of lipid membranes by propagating lipid peroxidation and facilitated ferroptotic cancer cell death initiated by erastin.In this work,singlet oxygen has been revealed to be a new reactive species that participates in ferroptosis,thus improving the understanding on iron-dependent lipid peroxidation and the mechanism of ferroptosis.展开更多
Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The prim...Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.展开更多
Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox...Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.展开更多
Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a ...Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.展开更多
Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evoluti...Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.展开更多
Ferroptosis is defined as an iron-dependent form of regulated cell death that is initiated by the toxic accumulation of lipid peroxides on cellular membranes.In the past decade,ferroptosis has aroused considerable int...Ferroptosis is defined as an iron-dependent form of regulated cell death that is initiated by the toxic accumulation of lipid peroxides on cellular membranes.In the past decade,ferroptosis has aroused considerable interest in comprehensive treatment of colorectal cancer,mainly as it is a specific cell death mode that is mechanistically and morphologically differ from other forms of cell death such as autophagy,apoptosis,and pyroptosis,following by holding a giant potential for the therapy of colorectal cancer.Research has found that various active ingredients in traditional Chinese medicine possess the ability of inducing ferroptosis in colorectal cancer cells through pathways such as lipid metabolism,iron metabolism,or cysteine/glutamate transporter system,which demonstrating enormous clinical therapeutic potential.In this review,the metabolic regulatory network of ferroptosis is introduced from the perspective of ferroptosis mechanism,and the information on the induction of ferroptosis in colorectal cancer cells by active ingredients of traditional Chinese medicine is also be retrospected,which the purpose is to provide novel strategies for the anti-colorectal cancer therapy of active ingredients in traditional Chinese medicine.展开更多
Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransfera...Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C(CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene m RNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.展开更多
Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62...Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62±1.04 kg)were assigned within sex and weight blocks to a 2×3 factorial arrangement using 48 pens with 4 pigs per pen.Dietary treatments consisted of lipid peroxidation(6%edible soybean oil or 6%peroxidized soybean oil),and antioxidant supplementation(control diet containing 33 IU/kg DL-α-tocopheryl-acetate;control with 200 IU/kg additional dl-α-tocopheryl-acetate;or control with 400 mg/kg polyphenols).Pigs were fed in 2 phases for 14 and 21 days,respectively.Results:Peroxidation of oil for 12 days at 80°C with exposure to 50 L/min of air substantially increased peroxide values,anisidine value,hexanal,and 2,4-decadienal concentrations.Feeding peroxidized lipids decreased(P<0.001)body weight(23.16 vs.18.74 kg),daily gain(473 vs.346 g/d),daily feed intake(658 vs.535 g/d)and gain:feed ratio(719 vs.647 g/kg).Lipid peroxidation decreased serum vitamin E(P<0.001)and this decrease was larger on day 35(1.82 vs.0.81 mg/kg)than day 14(1.95 vs.1.38 mg/kg).Supplemental vitamin E,but not polyphenols,increased(P≤0.002)serum vitamin E by 84%and 22%for control and peroxidized diets,respectively(interaction,P=0.001).Serum malondialdehyde decreased(P<0.001)with peroxidation on day 14,but not day 35 and protein carbonyl increased(P<0.001)with peroxidation on day 35,but not day 14.Serum 8-hydroxydeoxyguanosine was not affected(P>0.05).Total antioxidant capacity decreased with peroxidation(P<0.001)and increased with vitamin E(P=0.065)and polyphenols(P=0.046)for the control oil diet only.Serum cytokine concentrations increased with feeding peroxidized lipids on day 35,but were not affected by antioxidant supplementation(P>0.05).Conclusion:Feeding peroxidized lipids negatively impacted growth performance and antioxidant capacity of nursery pigs.Supplementation of vitamin E and polyphenols improved total antioxidant capacity,especially in pigs fed control diets,but did not restore growth performance.展开更多
OBJECTIVE N2L is a novel lipoic acid-niacin dimer regulating lipid metabolism with multifunction,including antioxidant effect.We investigated the protective effect of N2L and the underlying mechanisms under the ferrop...OBJECTIVE N2L is a novel lipoic acid-niacin dimer regulating lipid metabolism with multifunction,including antioxidant effect.We investigated the protective effect of N2L and the underlying mechanisms under the ferroptosis inducer RAS-selective lethality 3(RSL3)treat⁃ment in HT22 cells.METHODS HT22 cells were pretreated with N2L and then were treated with RSL3 to establish a ferroptosis cell model.MTT assay was used to detect the cell survival rate.Free radical probe(dihydroethidium,DHE)and ferrous probe FerroOrange were used to detect the contents of free radicals and ferrous ions in cells.The ultrastructure of mitochondria of treat⁃ed cells was observed by transmission electron microscope.The expression of ferroptosis-relat⁃ed proteins acyl-CoA synthetase long-chain family member 4(ACSL4),glutathione peroxidase 4(GPX4),cyclooxygenase-2(COX-2),ferritin Heavy Chain 1(FTH1),nuclear factor E2-related factor 2/heme oxygenase-1,and phosphoryla⁃tion levels of the c-Jun N-terminal kinase(JNK)/extracellular regulated protein kinases(ERK)pathway were detected by Western blotting.RE⁃SULTS RSL3 decreased the cell viability and induced excessive accumulation of(reactive oxy⁃gen species)ROS in HT22 cells.N2L pretreat⁃ment effectively protected HT22 cells against lipid peroxidation.What′s more,N2L recovered GPX4 protein expression and blocked the increase of COX-2 and ACSL4 expressions.Moreover,N2L also significantly prevented FTH1 from downregulation and maintained iron homeo⁃stasis.Finally,N2L pretreatment could decrease JNK/ERK activation induced by RSL3.CON⁃CLUSION N2L is an excellent ferroptosis inhibi⁃tor,and its anti-ferroptosis mechanism may be related to the reduction of lipid peroxidation and the regulation of iron homeostasis.展开更多
<span style="font-family:Verdana;">The effects of each of the flavonoids;genistein (G), quercetin (Q) and</span><span style="font-family:""><span style="font-family:V...<span style="font-family:Verdana;">The effects of each of the flavonoids;genistein (G), quercetin (Q) and</span><span style="font-family:""><span style="font-family:Verdana;"> kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. </span><span style="font-family:Verdana;">The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest</span><span style="font-family:Verdana;"> levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.</span></span>展开更多
Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we ...Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.展开更多
Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotectiv...Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.展开更多
Spinal cord injury is characte rized by diffe rent aetiologies,complex pathogenesis,and diverse pathological changes.Current treatments are not ideal,and prognosis is generally poor.After spinal cord injury,neurons di...Spinal cord injury is characte rized by diffe rent aetiologies,complex pathogenesis,and diverse pathological changes.Current treatments are not ideal,and prognosis is generally poor.After spinal cord injury,neurons die due to various forms of cell death.Among them,fe rroptosis causes dysfunction after spinal cord injury,and no existing traditional treatments have been indicated to block its occurrence.Meanwhile,emerging therapies using mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation therapy are promising for reve rsing spinal co rd neuronal ferroptosis after spinal cord injury.However,no definitive studies have demonstrated the effectiveness of these approaches.This review summarizes the existing research on the mechanisms of ferroptosis;fe rroptosis after spinal cord injury;treatment of spinal cord injury with mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation;and treatment of ferroptosis using mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation.Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury.In addition,mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation can reve rse adverse outcomes of spinal cord injury and regulate ferroptosis-related fa ctors.Thus,it can be inferred that mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation have the potential to inhibit fe rroptosis after spinal cord injury.This review serves as a reference for future research to confirm these conclusions.展开更多
基金supported by FIS PI16/00786(2016)and FIS PI19/00377(2019)grantsthe Ministerio de Sanidad,Spain and the Fondo Europeo de Desarrollo Regional(FEDER Unión Europea)Spanish Ministry of Education,Culture and Sport.This activity has been co-financed by the European Regional Development Fund(ERDF)and by the Regional Ministry of Economic Transformation,Industry,Knowledge and Universities of the Junta de Andalucía,within the framework of the ERDF Andalusia operational program 2014-2020 Thematic objective“01-Reinforcement of research,technological development and innovation”through the reference research project CTS-5725 and PY18-850(to JASA).
文摘Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation disorders.Mitochondrial dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders.Currently,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear.In this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular function.The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration.Therefore,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration.In addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.
基金supported in part by the National Natural Science Foundation of China(32172311)Key-Area Research and Development Program of Guangdong Province(2019B020213001)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515012413)the support from the Instrumental Analysis Center of Shenzhen University(Xili Campus)。
文摘This study aimed to analyze the effect of lipid peroxidation on the allergenicity and functional properties of soybeanβ-conglycinin(7 S)and glycinin(11 S).Oxidation complexes were determined using the lipid peroxidation method.Functional properties were analyzed based on emulsifying and foaming properties.The potential allergenicity was evaluated by in vitro and in vivo methods.The results found that oxidation altered structures of the proteins and resulted in the formation of cross-linked protein polymers.The emulsion and foaming properties of the proteins were improved after oxidation.The IgE-binding capacity of 7 S and11 S reduced after oxidation.KU812 cell assays showed that both histamine and IL-4 release decreased after oxidation treatment.A mouse model showed that oxidation reduced the IgE,IgG,and IgG1 levels,as well as reduced histamine and mMCP-1 release in serum,which might suppress the allergic reaction.In conclusion,the lipid peroxidation treatment likely causes changes to the functional properties of soybean,decreasing the potential allergenicity of 7 S and 11 S.
文摘Heavy metals have harmful effects on human health,and exposure to these metals has been increased by industrial and anthropogenic activities and modern industrialization.Heavy metals content of the liver tissues was determine d using Atomic Absorption Spectrophotometer method,while lipid peroxidation was carried out.Heavy metals analyzed include;lead(Pb),cadmium(Cd),zinc(Zn),Arsenic(As),and Mercury(Hg).The findings revealed that the heavy metal Zinc(Zn)has high concentrations in the muscles of the fish species,the concentration of this heavy metal Zinc is high in River Gindin Dorowa th a n in River Ibi and River Donga shows less concentration of this heavy metal though it’s above WHO permissible limits.Results revealed that only Zn and Cd were present in the muscle from the three rivers.Pb was found only in the liver from Gindin-Dorowa at the concentration of 0.017 mg/kg,which is not significant(P<0.05)when compared with other locations,while Hg and As were absent in all the muscle samples.The highest concentration of Zn was found in the muscle sample from Gindin-Dorowa(7.450 mg/kg)followed by Ibi(6.16 mg/kg)and the least being Donga(4.365 mg/kg)which are significantly(P<0.05)different from one another.However,there was no significant(P<0.05)difference among the Cd composition of muscle from Gindin-Dorowa(0.025 mg/kg),Donga(0.024 mg/kg)and Ibi(0.015 mg/kg),respectively.The TBA was found in the hepatic tissue sample from Gidin-Dorowa,which has the highest Zn,Cd and no Pb content,followed by Ibi and then the Donga sample.This suggests that there is a positive relationship between heavy metals and the effect of TBA on the hepatic tissues,justifying the fact that heavy metals affect the hepatic tissues of fish,while on the cerebral tissue.In conclusion,it revealed that there is a negative relation between heavy metals and the effect of TBA on the cerebral tissues to protect or save aquatic habitat s of fish quality and aquatic life.
文摘Dietary omega-3 (n - 3) polyunsaturated fatty acids (PUFA) are recommended by public health organizations to reduce the risk of cardiovascular disease, and several epidemiological studies have suggested there is an inverse association between n - 3 intake and human cancers. However, n - 3 are susceptible to an increase in lipid peroxidation in the human body. As part of a crossover dietary intervention study of a diet (20% of energy from fat) with or without an additional 3% of energy from a mixture of n - 3 (with 5.36 g α-linolenic acid and 1.45 g eicosapentaenoic acid and docosahexaenoic acid per 2000 kcal per day), we measured total in vivo lipid peroxidation in healthy postmenopausal women (n = 15). Our results indicated that the diet with 3% of energy from n - 3 significantly increased the urinary concentrations of total polar lipophilic aldehydes and related compounds produced via lipid peroxidation (p α, β-unsaturated hydroxy aldehydes 4-hydroxy-2-trans - hexenal (p trans -decenal (p < 0.05) compared to the diet with less than 1% of energy from n - 3. This is also the first study to document the presence of 4-hydroxy-2-trans -decenal in the urine of individuals consuming n - 3. These results demonstrate that an increase in 3% of energy from dietary n – 3 increases in vivo lipid peroxidation.
文摘Lipoxidation is formed during the oxidation of lipids and specific proteins,causing an alteration in proteins function.Although this occurs under physiological conditions,in many cases,it has been associated with pathological processes,including cancer.Oxidative DNA damage is a significant contributor to cancer development,and lipoxidation products such as malondialdehyde(MDA)and 4-hydroxy-2-nonenal(4-HNE)play a role in the induction of mutations responsible for DNA modifications.Elevations of reactive aldehydes can be seen in patients with metastatic disease in comparison to those without metastatic disease.Lipoxidation adducts can modify the immune response,consequently causing either positive or negative alterations in cancer progression.When reactive aldehydes are added to tumor cells,they exert similar effects to chemotherapeutic drugs by forming DNA adducts and consequently steer the tumor cells toward apoptosis.This article highlights the role of botanical compounds in lipid metabolism,lipid peroxidation,and cell cycle arrest and discusses the potential role they may have in oncology treatments.
基金This work was supported by the National Natural Science Foundation of China(Grant No.20777040)the Ministry of Education,People’s Republic of China as a cultivation fund of the Key Scientific and Technical Innovation Project(No.707011)+1 种基金the specialized research fund for doctoral program of higher education(No.20070055031)the program of New Century Excellent Talent.
文摘The joint toxicity of Penta-BDE(Pe-BDE)and heavy metals including cadmium and copper on Daphnia magna(D.magna)was evaluated on the basis of determining the 48 h survival,antioxidative enzyme responses,and lipid peroxidation.The response was classified as additive,greater than additive,or less than additive by comparing the measured“toxic units,TU”with one.Based on the survival of D.magna,less-than-additive interactions were found in most of mixtures treatments.This may be attributed to the different toxicity mechanism between Pe-BDE and metals.Cu and Cd played a greater role in toxicity than what Pe-BDE did.As for the superoxide dismutase(SOD)and catalase(CAT)activity,most response was less than additive.For the glutathione S-transferases(GST)activity,most of the greater-thanadditive responses were found in the Cu plus Pe-BDE treatments,but the additive responses occurred in Cd plus Pe-BDE treatments and binary metal treatments.For lipid peroxide levels,which were measured as malondialdehyde(MDA)levels,less-than-additive response occurred in the 50%Cd plus 50%Cu and ternary mixture treatments.Results suggested that Pe-BDE,Cd,and Cu could induce different patterns of antioxidant enzyme responses,such as antioxidant/prooxidant responses,depending on their capability to produce reactive oxygen species and antioxidant enzymes to detoxify them.
文摘The germination of laser-irradiated Chinese pine seeds was carried out under drought stress.The activities of superoxide dismutase(SOD)and peroxidase(POD),and the content of malondialdehyde(MDA)were determined.Results showed notably increased germination percentage,root length,vitality index and fresh weight.The SOD and POD protective enzyme system activity of the Chinese pine seedlings obviously rose.It can be concluded that the germi-nation and juvenile resistance of Chinese pine seeds under drought stress are enhanced after laser processing.
基金the National Science Fund for Distinguished Young Scholars(Grant No.22025406)the National Natural Science Foundation of China(Grants No.21874125,22074138)+1 种基金Science and Technology Innovation Foundation of Jilin Province(Grants No.20190201074JC,20200703021ZP)the Youth Innovation Promotion Association of CAS(Grant No.2020233).
文摘Ferroptosis is a cell death pathway mediated by iron-dependent accumulation of lipid peroxide.However,the specific downstream molecular events of iron-dependent lipid peroxidation are yet to be elucidated.In this study,based on various spectral analyses,we have found evidence that singlet oxygen is produced through the Russell mechanism during the self-reaction of lipid peroxyl radicals generated via iron-dependent lipid peroxidation regardless of the presence of cholesterol.Significantly reduced generation of singlet oxygen was observed in the absence of iron.The generated singlet oxygen accelerated the oxidative damage of lipid membranes by propagating lipid peroxidation and facilitated ferroptotic cancer cell death initiated by erastin.In this work,singlet oxygen has been revealed to be a new reactive species that participates in ferroptosis,thus improving the understanding on iron-dependent lipid peroxidation and the mechanism of ferroptosis.
基金supported by the National Natural Science Foundation of China,Nos.82071339 and 82271370(both to LG).
文摘Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.
文摘Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.
基金supported by grants from Jiangsu Commission of Health,No.Z2021086(to XL)Science and Technology Program of Suzhou,Nos.SYSD2020008(to XL),SKYD2022012(to XL)+1 种基金Suzhou Municipal Health Commission,No.KJXW2020058(to XL)Science and Technology Program of Zhangjiagang,No.ZKS2018(to XL)。
文摘Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81501106(to CF)Fund of Taishan Scholar Project(to CF)+1 种基金the Natural Science Foundation of Shandong Province,No.ZR2020QH106(to YH)the Medical and Health Science and Technology Development Plan of Shandong Province,No.202203010799(to QS)。
文摘Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.
基金supported by the National Natural Science Foundation of China (82304789)Key Research and Development Program of the Science and Technology Department of Sichuan Province (2023YFS0110)+2 种基金China Postdoctoral Science Foundation (2022M720670)Postdoctoral Program of Sichuan Academy of Medical Sciences (2022BH011)Sichuan Provincial Medical Youth Innovation Research Project (Q22007).
文摘Ferroptosis is defined as an iron-dependent form of regulated cell death that is initiated by the toxic accumulation of lipid peroxides on cellular membranes.In the past decade,ferroptosis has aroused considerable interest in comprehensive treatment of colorectal cancer,mainly as it is a specific cell death mode that is mechanistically and morphologically differ from other forms of cell death such as autophagy,apoptosis,and pyroptosis,following by holding a giant potential for the therapy of colorectal cancer.Research has found that various active ingredients in traditional Chinese medicine possess the ability of inducing ferroptosis in colorectal cancer cells through pathways such as lipid metabolism,iron metabolism,or cysteine/glutamate transporter system,which demonstrating enormous clinical therapeutic potential.In this review,the metabolic regulatory network of ferroptosis is introduced from the perspective of ferroptosis mechanism,and the information on the induction of ferroptosis in colorectal cancer cells by active ingredients of traditional Chinese medicine is also be retrospected,which the purpose is to provide novel strategies for the anti-colorectal cancer therapy of active ingredients in traditional Chinese medicine.
基金supported by the National Key Research and Development Program of China (Grant No. 2017YFE0109900)the National Natural Science Foundation of China (Grant Nos. 82025034 and 81973392)+5 种基金the Shenzhen Science and Technology Program (Grant No. KQTD20190929174023858)the Natural Science Foundation of Guangdong (Grant No. 2017A030311018)the 111 project (Grant No. B16047)the Key Laboratory Foundation of Guangdong Province (Grant No. 2017B030314030)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (Grant No. 2017BT01Y093)the National Engineering and Technology Research Center for New drug Druggability Evaluation (Seed Program of Guangdong Province, Grant No. 2017B090903004)。
文摘Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C(CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene m RNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.
基金the Peruvian National Fund,for Scientific,Technological,and Technological Innovation Development(FONDECYT)the funding branch of the National Council for Science,Technological,and Technological Innovation Development(CONCYTEC)Peru(grant contract N°233-2015-FONDECYT)for providing a doctoral scholarship to Ysenia Victoria Silva-Guillen.
文摘Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62±1.04 kg)were assigned within sex and weight blocks to a 2×3 factorial arrangement using 48 pens with 4 pigs per pen.Dietary treatments consisted of lipid peroxidation(6%edible soybean oil or 6%peroxidized soybean oil),and antioxidant supplementation(control diet containing 33 IU/kg DL-α-tocopheryl-acetate;control with 200 IU/kg additional dl-α-tocopheryl-acetate;or control with 400 mg/kg polyphenols).Pigs were fed in 2 phases for 14 and 21 days,respectively.Results:Peroxidation of oil for 12 days at 80°C with exposure to 50 L/min of air substantially increased peroxide values,anisidine value,hexanal,and 2,4-decadienal concentrations.Feeding peroxidized lipids decreased(P<0.001)body weight(23.16 vs.18.74 kg),daily gain(473 vs.346 g/d),daily feed intake(658 vs.535 g/d)and gain:feed ratio(719 vs.647 g/kg).Lipid peroxidation decreased serum vitamin E(P<0.001)and this decrease was larger on day 35(1.82 vs.0.81 mg/kg)than day 14(1.95 vs.1.38 mg/kg).Supplemental vitamin E,but not polyphenols,increased(P≤0.002)serum vitamin E by 84%and 22%for control and peroxidized diets,respectively(interaction,P=0.001).Serum malondialdehyde decreased(P<0.001)with peroxidation on day 14,but not day 35 and protein carbonyl increased(P<0.001)with peroxidation on day 35,but not day 14.Serum 8-hydroxydeoxyguanosine was not affected(P>0.05).Total antioxidant capacity decreased with peroxidation(P<0.001)and increased with vitamin E(P=0.065)and polyphenols(P=0.046)for the control oil diet only.Serum cytokine concentrations increased with feeding peroxidized lipids on day 35,but were not affected by antioxidant supplementation(P>0.05).Conclusion:Feeding peroxidized lipids negatively impacted growth performance and antioxidant capacity of nursery pigs.Supplementation of vitamin E and polyphenols improved total antioxidant capacity,especially in pigs fed control diets,but did not restore growth performance.
文摘OBJECTIVE N2L is a novel lipoic acid-niacin dimer regulating lipid metabolism with multifunction,including antioxidant effect.We investigated the protective effect of N2L and the underlying mechanisms under the ferroptosis inducer RAS-selective lethality 3(RSL3)treat⁃ment in HT22 cells.METHODS HT22 cells were pretreated with N2L and then were treated with RSL3 to establish a ferroptosis cell model.MTT assay was used to detect the cell survival rate.Free radical probe(dihydroethidium,DHE)and ferrous probe FerroOrange were used to detect the contents of free radicals and ferrous ions in cells.The ultrastructure of mitochondria of treat⁃ed cells was observed by transmission electron microscope.The expression of ferroptosis-relat⁃ed proteins acyl-CoA synthetase long-chain family member 4(ACSL4),glutathione peroxidase 4(GPX4),cyclooxygenase-2(COX-2),ferritin Heavy Chain 1(FTH1),nuclear factor E2-related factor 2/heme oxygenase-1,and phosphoryla⁃tion levels of the c-Jun N-terminal kinase(JNK)/extracellular regulated protein kinases(ERK)pathway were detected by Western blotting.RE⁃SULTS RSL3 decreased the cell viability and induced excessive accumulation of(reactive oxy⁃gen species)ROS in HT22 cells.N2L pretreat⁃ment effectively protected HT22 cells against lipid peroxidation.What′s more,N2L recovered GPX4 protein expression and blocked the increase of COX-2 and ACSL4 expressions.Moreover,N2L also significantly prevented FTH1 from downregulation and maintained iron homeo⁃stasis.Finally,N2L pretreatment could decrease JNK/ERK activation induced by RSL3.CON⁃CLUSION N2L is an excellent ferroptosis inhibi⁃tor,and its anti-ferroptosis mechanism may be related to the reduction of lipid peroxidation and the regulation of iron homeostasis.
文摘<span style="font-family:Verdana;">The effects of each of the flavonoids;genistein (G), quercetin (Q) and</span><span style="font-family:""><span style="font-family:Verdana;"> kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. </span><span style="font-family:Verdana;">The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest</span><span style="font-family:Verdana;"> levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.</span></span>
基金supported by the National Natural Science Foundation of China,No.81971425the Natural Science Foundation of Zhejiang Province,No.LY20H040002(both to XQF).
文摘Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.
基金supported by the National Natural Science Foundation of China,Nos.81871785 and 81672161(both to ZSY)。
文摘Ferroptosis is one of the critical pathological events in spinal cord injury.Erythropoietin has been reported to improve the recovery of spinal cord injury.However,whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined.In this study,we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks.Both low and high doses of erythropoietin promoted recovery of hindlimb function,and the high dose of erythropoietin led to better outcome.High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin.The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1(a ferroptosis suppressor),and the effects of erythropoietin were largely diminished by RSL3(ferroptosis activator).In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4.This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury.Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.
基金supported by a grant from funded by the National Natural Science Foundation of China (Youth Program),No.81101462Natural Science Foundation of Liaoning Province,Nos.2016028 75 and 2019-KF-01-06+1 种基金Liaoning Provincial Public Welfare Science,No.2016003001University of China Medical University Discipline Development Project,No.112-3110119071 (all to LXZ)。
文摘Spinal cord injury is characte rized by diffe rent aetiologies,complex pathogenesis,and diverse pathological changes.Current treatments are not ideal,and prognosis is generally poor.After spinal cord injury,neurons die due to various forms of cell death.Among them,fe rroptosis causes dysfunction after spinal cord injury,and no existing traditional treatments have been indicated to block its occurrence.Meanwhile,emerging therapies using mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation therapy are promising for reve rsing spinal co rd neuronal ferroptosis after spinal cord injury.However,no definitive studies have demonstrated the effectiveness of these approaches.This review summarizes the existing research on the mechanisms of ferroptosis;fe rroptosis after spinal cord injury;treatment of spinal cord injury with mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation;and treatment of ferroptosis using mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation.Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury.In addition,mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation can reve rse adverse outcomes of spinal cord injury and regulate ferroptosis-related fa ctors.Thus,it can be inferred that mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation have the potential to inhibit fe rroptosis after spinal cord injury.This review serves as a reference for future research to confirm these conclusions.
