{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:20:02Z","timestamp":1791685202527,"version":"4.3.4"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jagiellonian University, Medical College","award":["N41\/DBS\/001389"],"award-info":[{"award-number":["N41\/DBS\/001389"]}]},{"name":"Priority Area qLIFE","award":["N41\/DBS\/001389"],"award-info":[{"award-number":["N41\/DBS\/001389"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: The role of sulfur-containing drugs, disulfiram (DSF) and N-acetylcysteine (NAC), in alleviating neuroinflammation is poorly understood. The objective of this study was to examine the effect of DSF and NAC on memory and on the metabolism of L-cysteine and inflammation-related parameters in the cerebral cortex of rats in a model of neuroinflammation induced by the administration of lipopolysaccharide (LPS). Methods: All the treatments were administered intraperitoneally for 10 days (LPS at a dose of 0.5 mg\/kg b.w., DSF at a dose of 100 mg\/kg b.w, and NAC at a dose of 100 mg\/kg b.w.). Behavior was evaluated by the novel object recognition (NOR) test and object location (OL) test, and the level of brain-derived neurotrophic factor (BDNF) was assayed to evaluate neuronal functioning. Cerebral cortex homogenates were tested for hydrogen sulfide (H2S), sulfane sulfur, sulfates, non-protein sulfhydryl groups (NPSH), nitric oxide (NO), and reactive oxygen species (ROS) by biochemical analysis. Results: Neither DSF nor NAC alleviated LPS-induced memory disorders estimated by the NOR test and OL test. The studied compounds also did not affect significantly the levels of BDNF, ROS, NO, H2S, and sulfane sulfur in the cerebral cortex. However, we observed an increase in sulfate concentration in brain tissues after LPS treatment, while DSF and NAC caused an additional increase in sulfate concentration. On the other hand, our study showed that the administration of DSF or NAC together with LPS significantly enhanced the cortical level of NPSH, of which glutathione is the main component. Conclusions: Our study did not confirm the suggested potential of DSF and NAC to correct memory disorders; however, it corroborated the notion that they reduced oxidative stress induced by LPS by increasing the NPSH level. Additionally, our study showed an increase in sulfate concentration in the brain tissues after LPS treatment, which means the upregulation of sulfite and sulfate production in inflammatory conditions.<\/jats:p>","DOI":"10.3390\/molecules30030578","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T11:38:49Z","timestamp":1737977929000},"page":"578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Effect of Disulfiram and N-Acetylcysteine, Potential Compensators for Sulfur Disorders, on Lipopolysaccharide-Induced Neuroinflammation Leading to Memory Impairment and the Metabolism of L-Cysteine Disturbance"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0422-0428","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Iciek","sequence":"first","affiliation":[{"name":"Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, PL 31-034 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-6292","authenticated-orcid":false,"given":"Anna","family":"Bilska-Wilkosz","sequence":"additional","affiliation":[{"name":"Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, PL 31-034 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6393-9977","authenticated-orcid":false,"given":"Magdalena","family":"G\u00f3rny","sequence":"additional","affiliation":[{"name":"Chair of Medical Biochemistry, Jagiellonian University Medical College, Kopernika 7, PL 31-034 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Bednarski","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Zygmunt","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthea","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Cracow, Poland"},{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9453-1237","authenticated-orcid":false,"given":"Noemi","family":"Nicosia","sequence":"additional","affiliation":[{"name":"PhD Program in Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia Pia","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Zammit","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Cracow, Poland"},{"name":"Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3946-1192","authenticated-orcid":false,"given":"Magdalena","family":"Kota\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Screening, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s12974-015-0434-1","article-title":"Lipopolysaccharide-induced blood-brain barrier disruption: Roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit","volume":"12","author":"Banks","year":"2015","journal-title":"J. Neuroinflam."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neulet.2018.09.010","article-title":"Peucedani Japonici Radix ameliorates lipopolysaccharide-induced neuroinflammation by regulating microglial responses","volume":"686","author":"Ju","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s00210-016-1234-6","article-title":"Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress","volume":"389","author":"Ali","year":"2016","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jnutbio.2018.01.009","article-title":"Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress","volume":"56","author":"Wang","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.33549\/physiolres.933480","article-title":"Lipopolysaccharide-induced memory impairment in rats: A model of Alzheimer\u2019s disease","volume":"66","author":"Zakaria","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator","volume":"16","author":"Abe","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.nlm.2013.05.006","article-title":"Hydrogen sulfide slows down progression of experimental Alzheimer\u2019s disease by targeting multiple pathophysiological mechanisms","volume":"104","author":"Giuliani","year":"2013","journal-title":"Neurobiol. Learn Mem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1096\/fj.12-226415","article-title":"Polysulfides are possible H2S-derived signaling molecules in rat brain","volume":"27","author":"Kimura","year":"2013","journal-title":"FASEB J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1007\/s12640-021-00374-6","article-title":"Hydrogen Sulfide Ameliorates Lipopolysaccharide-Induced Memory Impairment in Mice by Reducing Apoptosis, Oxidative, and Inflammatory Effects","volume":"39","author":"Kshirsagar","year":"2021","journal-title":"Neurotox. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.freeradbiomed.2017.10.346","article-title":"Analysis of endogenous H2S and H2Sn in mouse brain by high-performance liquid chromatography with fluorescence and tandem mass spectrometric detection","volume":"113","author":"Koike","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1089\/ars.2020.8073","article-title":"High-Precision Sulfur Metabolomics Innovated by a New Specific Probe for Trapping Reactive Sulfur Species","volume":"34","author":"Kasamatsu","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.freeradbiomed.2009.09.018","article-title":"Making and working with hydrogen sulfide: The chemistry and generation of hydrogen sulfide in vitro and its measurement in vivo: A review","volume":"47","author":"Hughes","year":"2009","journal-title":"Free Radical Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Iciek, M., Bilska-Wilkosz, A., Kozdrowicki, M., and G\u00f3rny, M. (2022). Reactive sulfur species and their significance in health and disease. Biosci. Rep., 42.","DOI":"10.1042\/BSR20221006"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rodrigues, F.S., Souza, M.A., Magni, D.V., Ferreira, A.P.O., Mota, B.C., Cardoso, A.M., Paim, M., Xavier, L.L., Ferreira, J., and Schetinger, M.R. (2013). N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078332"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cbi.2010.04.011","article-title":"N-acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium","volume":"186","author":"Fiorenza","year":"2010","journal-title":"Chemico- Biol. Interact."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00213-017-4762-y","article-title":"Chronic N-acetylcysteine treatment alleviates acute lipopolysaccharide-induced working memory deficit through upregulating caveolin-1 and synaptophysin in mice","volume":"235","author":"Shen","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1203\/01.pdr.0000215045.91122.44","article-title":"Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats","volume":"59","author":"Jatana","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neubiorev.2017.04.013","article-title":"The effect of N-acetylcysteine (NAC) on human cognition\u2014A systematic review","volume":"78","author":"Skvarc","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107916","DOI":"10.1016\/j.pharmthera.2021.107916","article-title":"The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species","volume":"228","author":"Pedre","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1600-0447.1992.tb03309.x","article-title":"The pharmacology and toxicology of disulfiram and its metabolites","volume":"369","author":"Petersen","year":"1992","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref_21","first-page":"113","article-title":"Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents. Recent Pat","volume":"14","author":"Ekinci","year":"2019","journal-title":"Anti-Cancer Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shirley, D.A., Sharma, I., Warren, C.A., and Moonah, S. (2021). Drug Repurposing of the Alcohol Abuse Medication Disulfiram as an Anti-Parasitic Agent. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.633194"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s11739-021-02633-y","article-title":"COVID-19 and related symptoms in patients under disulfiram for alcohol use disorder","volume":"16","author":"Tamburin","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Iciek, M., Bilska-Wilkosz, A., Kozdrowicki, M., and G\u00f3rny, M. (2022). Reactive Sulfur Compounds in the Fight against COVID-19. Antioxidants, 11.","DOI":"10.3390\/antiox11061053"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e520","DOI":"10.1016\/S2352-3018(15)00226-X","article-title":"Short-term administration of disulfiram for reversal of latent HIV infection: A phase 2 dose-escalation study","volume":"2","author":"Elliott","year":"2015","journal-title":"Lancet HIV"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2306399120","DOI":"10.1073\/pnas.2306399120","article-title":"Disulfiram blocks inflammatory TLR4 signaling by targeting MD-2","volume":"120","author":"Bai","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Reinhardt, S., Stoye, N., Luderer, M., Kiefer, F., Schmitt, U., Lieb, K., and Endres, K. (2018). Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer\u2019s disease hallmarks. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19577-7"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zuhra, K., Panagaki, T., Randi, E.B., Augsburger, F., Blondel, M., Friocourt, G., Herault, Y., and Szabo, C. (2020). Mechanism of cystathionine-\u03b2-synthase inhibition by disulfiram: The role of bis(N,N-diethyldithiocarbamate)-copper(II). Biochemical Pharmacol., 182.","DOI":"10.1016\/j.bcp.2020.114267"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"577401","DOI":"10.1016\/j.jneuroim.2020.577401","article-title":"Repeated administration of LPS exaggerates amphetamine-induced locomotor response and causes learning deficits in mice","volume":"349","author":"Imbeault","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhao, J., Bi, W., Xiao, S., Lan, X., Cheng, X., Zhang, J., Lu, D., Wei, W., Wang, Y., and Li, H. (2019). Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42286-8"},{"key":"ref_31","first-page":"e58593","article-title":"Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget","volume":"141","author":"Denninger","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4103\/ijpvm.IJPVM_170_19","article-title":"Effect of Pentoxifylline on Apoptotic-Related Gene Expression Profile, Learning and Memory Impairment Induced by Systemic Lipopolysaccharide Administration in the Rat Hippocampus","volume":"11","author":"Akbari","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/1028415X.2022.2063578","article-title":"Neuropharmacological effects of honey in lipopolysaccharide-induced neuroinflammation, cognitive impairment, anxiety and motor impairment","volume":"26","author":"Adeniyi","year":"2023","journal-title":"Nutr. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s11011-018-0349-5","article-title":"Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: Insights into underlying molecular mechanisms","volume":"34","author":"Sadraie","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1007\/s11064-016-1881-5","article-title":"Protective effect of silibinin on learning and memory impairment in LPS-treated rats via ROS- BDNF-TrkB pathway","volume":"41","author":"Song","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1021\/acschemneuro.5b00274","article-title":"Perindopril attenuates lipopolysaccharide-induced amyloidogenesis and memory im- pairment by suppression of oxidative stress and RAGE activation","volume":"7","author":"Goel","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.pharep.2014.10.014","article-title":"Omega-3 fatty acids prevent LPS-induced passive avoidance learning and memory and CaMKII-alpha gene expression impairments in hippocampus of rat","volume":"67","author":"Dehkordi","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.bbi.2007.08.014","article-title":"Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system","volume":"22","author":"Chen","year":"2008","journal-title":"Brain Behav. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1055\/s-0042-103592","article-title":"Current findings and mechanisms of action of disulfiram in the treatment of alcohol dependence","volume":"49","author":"Mutschler","year":"2016","journal-title":"Pharmacopsychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1530-0277.1980.tb04841.x","article-title":"Disulfiram distribution and elimination in the rat after oral and intraperitoneal administration","volume":"4","author":"Faiman","year":"1980","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/0028-3908(83)90055-2","article-title":"Distribution of disulfiram in brain after carotid ligation in gerbils","volume":"9","author":"Gunasekaran","year":"1983","journal-title":"Neuropharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1600-0447.1992.tb03310.x","article-title":"A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites","volume":"369","author":"Johansson","year":"1992","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.18632\/oncotarget.23320","article-title":"Brain- and brain tumor-penetrating disulfiram nanoparticles: Sequence of cytotoxic events and efficacy in human glioma cell lines and intracranial xenografts","volume":"9","author":"Madala","year":"2017","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cbi.2016.04.026","article-title":"N-acetylcysteine protects memory decline induced by streptozotocin in mice","volume":"253","author":"Costa","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"More, J., Galusso, N., Veloso, P., Montecinos, L., Finkelstein, J.P., Sanchez, G., Bull, R., Vald\u00e9s, J.L., Hidalgo, C., and Paula-Lima, A. (2018). N-Acetylcysteine Prevents the Spatial Memory Deficits and the Redox-Dependent RyR2 Decrease Displayed by an Alzheimer\u2019s Disease Rat Model. Front. Aging Neurosci., 10.","DOI":"10.3389\/fnagi.2018.00399"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1016\/j.bbagen.2013.04.016","article-title":"The chemistry and biological activities of N-acetylcysteine","volume":"1830","author":"Samuni","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1054-3589(08)61042-X","article-title":"Aminoacylases","volume":"27","author":"Anders","year":"1994","journal-title":"Adv. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/j.1471-4159.1982.tb12548.x","article-title":"Cysteine and cystine transport at the blood-brain barrier","volume":"37","author":"Wade","year":"1981","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1007\/s13311-023-01422-z","article-title":"N-Acetylcysteine and Probenecid Adjuvant Therapy for Traumatic Brain Injury","volume":"6","author":"Clark","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1021\/acschemneuro.3c00180","article-title":"Role of Imaging Modalities and N-Acetylcysteine Treatment in Sepsis-Associated Encephalopathy","volume":"14","author":"Zhong","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Huang, S.F., Othman, A., Koshkin, A., Fischer, S., Fischer, D., Zamboni, N., Ono, K., Sawa, T., and Ogunshola, O.O. (2020). Astrocyte Glutathione Maintains Endothelial Barrier Stability. Redox. Biol., 34.","DOI":"10.1016\/j.redox.2020.101576"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1023\/A:1021191729865","article-title":"Potential role of cerebral glutathione in the maintenance of blood-brain barrier integrity in rat","volume":"12","author":"Agarwal","year":"1999","journal-title":"Neurochem. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sakai, M., Yu, Z., Taniguchi, M., Picotin, R., Oyama, N., Stellwagen, D., Ono, C., Kikuchi, Y., Matsui, K., and Nakanishi, M. (2023). N-Acetylcysteine Suppresses Microglial Inflammation and Induces Mortality Dose-Dependently via Tumor Necrosis Factor-\u03b1 Signaling. Int. J. Mol. Sci., 4.","DOI":"10.3390\/ijms24043798"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1007\/s11064-024-04105-z","article-title":"MM165\u2014A Small Hybrid Molecule Modulates the Kynurenine Pathway and Attenuates Lipopolysaccharide-Induced Memory Deficits and Inflammation","volume":"49","author":"Bednarski","year":"2024","journal-title":"Neurochem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.eatbeh.2014.10.008","article-title":"Disulfiram for binge eating disorder: An open trail","volume":"16","author":"Farci","year":"2015","journal-title":"Eat. Behav."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1007\/s10637-022-01271-1","article-title":"Phase II study of Disulfiram and Cisplatin in Refractory Germ Cell Tumors. The GCT-SK-006 phase II trial","volume":"40","author":"Mego","year":"2022","journal-title":"Investig. New Drugs."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.nlm.2007.08.018","article-title":"BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?","volume":"89","author":"Lu","year":"2008","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5604\/20831862.1163692","article-title":"Long-term treadmill exercise improves spatial memory of male APPswe\/PS1dE9 mice by regulation of BDNF expression and microglia activation","volume":"32","author":"Xiong","year":"2015","journal-title":"Biol. Sport."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Tsai, C.-Y., Chan, J.Y., Hsu, K., Chang, A.Y., and Chan, S.H. (2012). Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033527"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e696","DOI":"10.1038\/tp.2015.183","article-title":"Brain plasticity and cognitive functions after ethanol consumption in C57BL\/6 J mice","volume":"5","author":"Stragier","year":"2015","journal-title":"Transl. Psych."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.npep.2015.09.003","article-title":"LPS reduces BDNF and VEGF expression in the structures of the HPA axis of chronic social stressed female rats","volume":"54","author":"Nowacka","year":"2015","journal-title":"Neuropeptides"},{"key":"ref_62","first-page":"102","article-title":"Fundamental role of pan-inflammation and oxidative-nitrosative pathways in neuropathogenesis of Alzheimer\u2019s disease in focal cerebral ischemic rats","volume":"5","author":"Daulatzai","year":"2016","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100091","DOI":"10.1016\/j.crphar.2022.100091","article-title":"Dihydroquercetin ameliorates LPS-induced neuroinflammation and memory deficit","volume":"3","author":"Alam","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"115071","DOI":"10.1016\/j.ejmech.2022.115071","article-title":"Hybrid molecules combining GABA-A and serotonin 5-HT6 receptors activity designed to tackle neuroinflammation associated with depression","volume":"247","author":"Marcinkowska","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.00029.2006","article-title":"Nitric oxide and peroxynitrite in health and disease","volume":"87","author":"Pacher","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1038\/jcbfm.2011.48","article-title":"Neuro-oxidative-nitrosative stress in sepsis","volume":"31","author":"Berg","year":"2011","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s11481-020-09920-z","article-title":"Hydrogen Sulfide Reverses LPS-Induced Behavioral Deficits by Suppressing Microglial Activation and Promoting M2 Polarization","volume":"16","author":"Kumar","year":"2021","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"175743","DOI":"10.1016\/j.ejphar.2023.175743","article-title":"Hydrogen sulfide inhibits lipopolysaccharide-based neuroinflammation-induced astrocyte polarization after cerebral ischemia\/reperfusion injury","volume":"949","author":"Li","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neures.2023.07.004","article-title":"A novel hydrogen sulfide donor reduces neuroinflammation and seizures by activating ATP-sensitive potassium channels","volume":"199","author":"Kang","year":"2024","journal-title":"Neurosci. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0006-2952(00)00435-4","article-title":"Role of disulfiram in the in vitro inhibition of rat liver mitochondrial aldehyde dehydrogenase","volume":"60","author":"Shen","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"338","DOI":"10.2174\/156800911794519798","article-title":"Disulfiram, and disulfiram derivatives as novel potential anticancer drugs targeting the ubiquitin-proteasome system in both preclinical and clinical studies","volume":"11","author":"Kona","year":"2011","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.freeradbiomed.2015.10.410","article-title":"Glutathione, glutathione disulfide, and S-glutathionylated proteins in cell cultures","volume":"89","author":"Giustarini","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12939","DOI":"10.1039\/D1SC03828A","article-title":"Leveraging an enzyme\/artificial substrate system to enhance cellular persulfides and mitigate neuroinflammation","volume":"12","author":"Bora","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1097\/01.shk.0000183393.83272.de","article-title":"Oxidative stress-dependent conversion of hydrogen sulfide to sulfite by activated neutrophils","volume":"6","author":"Mitsuhashi","year":"2005","journal-title":"Shock"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Li, L.-C., Chen, W.-Y., Chen, J.-B., Lee, W.-C., Chang, C.-C., Tzeng, H.-T., Huang, C.-C., Chang, Y.-J., and Yang, J.-L. (2021). The AST-120 Recovers uremic toxin-induced cognitive deficity via NLRP3 Inflammasome Pathway in Astrocytes and Microglia. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091252"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1165\/ajrcmb.17.2.2764","article-title":"Induction of cystine transport and other stress proteins by disulfiram: Effects on glutathione levels in cultured cells","volume":"2","author":"Deneke","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_77","first-page":"1974982","article-title":"Can Lipoic Acid Attenuate Cardiovascular Disturbances Induced by Ethanol and Disulfiram Administration Separately or Jointly in Rats?","volume":"2019","author":"Filipek","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/0006-8993(91)90915-I","article-title":"Action of a chronic disulfiram administration on memory decay and on central cholinergic and adrenergic systems","volume":"551","author":"Molinengo","year":"1991","journal-title":"Brain Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.pnpbp.2012.06.018","article-title":"N-acetylcysteine possesses antidepressant-like activity through reduction of oxidative stress: Behavioral and biochemical analyses in rats","volume":"39","author":"Smaga","year":"2012","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.phrs.2003.09.013","article-title":"The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS)","volume":"49","author":"Pata","year":"2004","journal-title":"Pharmacol. Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Bharani, K.L., Derex, R., Granholm, A.C., and Ledreux, A. (2017). A noradrenergic lesion aggravates the effects of systemic inflammation on the hippocampus of aged rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189821"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Dudek, M., Knutelska, J., Bednarski, M., Nowi\u0144ski, L., Zygmunt, M., Mordyl, B., G\u0142uch-Lutwin, M., Kazek, G., Sapa, J., and Pytka, K. (2015). A comparison of the anorectic effect and safety of the alpha2-adrenoceptor ligands guanfacine and yohimbine in rats with diet-induced obesity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141327"},{"key":"ref_83","first-page":"349","article-title":"Effect of ethanol treatment on indices of cumulative oxidative stress","volume":"270","author":"Bondy","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.freeradbiomed.2011.01.025","article-title":"Measurement of plasma hydrogen sulfide in vivo and in vitro","volume":"50","author":"Shen","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0076-6879(87)43009-7","article-title":"Sulfane sulfur","volume":"143","author":"Wood","year":"1987","journal-title":"Methods Enzym."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and non-protein sulfhydryl groups in tissue by Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/3\/578\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:08Z","timestamp":1759919828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/3\/578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":87,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["molecules30030578"],"URL":"https:\/\/doi.org\/10.3390\/molecules30030578","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]}}}