Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Neuropharmacology
  4. Volume 23, Issue 1
  5. Article
Volume 23, Issue 1
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Background

Cadmium chloride (Cd) is a pervasive environmental heavy metal pollutant linked to mitochondrial dysfunction, memory loss, and genetic disorders, particularly in the context of neurodegenerative diseases like Alzheimer's disease (AD).

Methods

This study investigated the neurotherapeutic potential of vitamin B6 (Vit. B6) in mitigating Cd-induced oxidative stress and neuroinflammation-mediated synaptic and memory dysfunction. Adult albino mice were divided into four groups: Control (saline-treated), Cd-treated, Cd+Vit. B6-treated, and Vit. B6 alone-treated. Cd and Vit. B6 were administered intraperitoneally, and behavioral tests (Morris Water Maze, Y-Maze) were conducted. Subsequently, western blotting, antioxidant assays, blood glucose, and hyperlipidemia assessments were performed.

Results

Cd-treated mice exhibited impaired cognitive function, while Cd+Vit. B6-treated mice showed significant improvement. Cd-induced neurotoxic effects, including oxidative stress and neuroinflammation, were observed, along with disruptions in synaptic proteins (SYP and PSD95) and activation of p-JNK. Vit. B6 administration mitigated these effects, restoring synaptic and memory deficits. Molecular docking and MD simulation studies confirmed Vit. B6's inhibitory effect on IL-1β, NRF2, and p-JNK proteins.

Conclusion

These results highlight Vit. B6 as a safe therapeutic supplement to mitigate neurodegenerative disorders, emphasizing the importance of assessing nutritional interventions for combating environmental neurotoxicity in the interest of public health.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X22999240730154422
2024-07-31
2025-04-03

  • From This Site

    /content/journals/cn/10.2174/1570159X22999240730154422
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SulakhiyaK. KiskuA. PaliwalR. GuptaD.K. YadavY. PalA. KumarS. Nanotechnology for Drug Delivery and Pharmaceuticals.Elsevier202313116310.1016/B978‑0‑323‑95325‑2.00023‑7
     [Google Scholar]
  2. FungT.C. OlsonC.A. HsiaoE.Y. Interactions between the microbiota, immune and nervous systems in health and disease.Nat. Neurosci.201720214515510.1038/nn.4476 28092661
     [Google Scholar]
  3. SiulyS. ZhangY. Medical big data: Neurological diseases diagnosis through medical data analysis.Data Sci. Eng.201612546410.1007/s41019‑016‑0011‑3
     [Google Scholar]
  4. Van SchependomJ. D’haeseleerM. Advances in neurodegenerative diseases.J. Clin. Med.20231251709
     [Google Scholar]
  5. MiglioreL. CoppedèF. Genetic and environmental factors in cancer and neurodegenerative diseases.Mutat. Res. Rev. Mutat. Res.20025122-313515310.1016/S1383‑5742(02)00046‑7 12464348
     [Google Scholar]
  6. ChuA. ThorneA. GuiteH. The impact on mental well‐being of the urban and physical environment: An assessment of the evidence.J. Public Ment. Health200432173210.1108/17465729200400010
     [Google Scholar]
  7. CleggJ. HollisC. MawhoodL. RutterM. Developmental language disorders – a follow‐up in later adult life. Cognitive, language and psychosocial outcomes.J. Child Psychol. Psychiatry200546212814910.1111/j.1469‑7610.2004.00342.x 15679523
     [Google Scholar]
  8. ZvěřováM. Clinical aspects of Alzheimer’s disease.Clin. Biochem.2019723610.1016/j.clinbiochem.2019.04.015 31034802
     [Google Scholar]
  9. WinbladB. PalmerK. KivipeltoM. JelicV. FratiglioniL. WahlundL.O. NordbergA. BäckmanL. AlbertM. AlmkvistO. AraiH. BasunH. BlennowK. De LeonM. DeCarliC. ErkinjunttiT. GiacobiniE. GraffC. HardyJ. JackC. JormA. RitchieK. Van DuijnC. VisserP. PetersenR.C. Mild cognitive impairment - beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment.J. Intern. Med.2004256324024610.1111/j.1365‑2796.2004.01380.x 15324367
     [Google Scholar]
  10. BalakrishnanR. KimY.S. KimG.W. KimW.J. HongS.M. KimC.G. ChoiD.K. Standardized extract of Glehnia littoralis abrogates memory impairment and neuroinflammation by regulation of CREB/BDNF and NF-κB/MAPK signaling in scopolamine-induced amnesic mice model.Biomed. Pharmacother.202316511510610.1016/j.biopha.2023.115106 37421783
     [Google Scholar]
  11. MecocciP. Oxidative stress in mild cognitive impairment and Alzheimer disease: A continuum.J. Alzheimers Dis.20046215916310.3233/JAD‑2004‑6207 15096699
     [Google Scholar]
  12. BaiR. GuoJ. YeX.Y. XieY. XieT. Oxidative stress: The core pathogenesis and mechanism of Alzheimer’s disease.Ageing Res. Rev.20227710161910.1016/j.arr.2022.101619 35395415
     [Google Scholar]
  13. OstrowskiR.P. PuckoE.B. Harnessing oxidative stress for anti-glioma therapy.Neurochem. Int.202215410528110.1016/j.neuint.2022.105281 35038460
     [Google Scholar]
  14. DengC. MengZ. ChenH. MengS. Tetramethylpyrazine ameliorates systemic streptozotocin-induced Alzheimer-like pathology.J. Chem. Neuroanat.202312710220710.1016/j.jchemneu.2022.102207 36470527
     [Google Scholar]
  15. WeilR.S. CostantiniA.A. SchragA.E. Mild cognitive impairment in Parkinson’s disease—what is it?Curr. Neurol. Neurosci. Rep.20181841710.1007/s11910‑018‑0823‑9 29525906
     [Google Scholar]
  16. BudsonA.E. SolomonP.R. Memory Loss, Alzheimer’s Disease, and Dementia-E-Book: A Practical Guide for Clinicians.Elsevier Health Sciences2021
     [Google Scholar]
  17. PandeyG. MadhuriS. Heavy metals causing toxicity in animals and fishes. Res. J. Animal.Vet. Fishery Sci.2014221723
     [Google Scholar]
  18. de VriesW. RömkensP.F. SchützeG. Critical soil concentrations of cadmium, lead, and mercury in view of health effects on humans and animals.Rev. Environ. Contam. Toxicol.200719191130 17708073
     [Google Scholar]
  19. OjoO.A. RotimiD.E. OjoA.B. OgunlakinA.D. AjiboyeB.O. Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats.Sci. Rep.2023131157710.1038/s41598‑023‑28893‑6 36709339
     [Google Scholar]
  20. SinghS. VrishniS. SinghB.K. RahmanI. KakkarP. Nrf2-ARE stress response mechanism: A control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases.Free Radic. Res.201044111267128810.3109/10715762.2010.507670 20815789
     [Google Scholar]
  21. DuaK. MalylaV. SinghviG. WadhwaR. KrishnaR.V. ShuklaS.D. ShastriM.D. ChellappanD.K. MauryaP.K. SatijaS. MehtaM. GulatiM. HansbroN. ColletT. AwasthiR. GuptaG. HsuA. HansbroP.M. Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems.Chem. Biol. Interact.201929916817810.1016/j.cbi.2018.12.009 30553721
     [Google Scholar]
  22. MooneyS. LeuendorfJ.E. HendricksonC. HellmannH. Vitamin B6: A long known compound of surprising complexity.Molecules200914132935110.3390/molecules14010329 19145213
     [Google Scholar]
  23. MaloufR. Grimley EvansJ. DementiaC. GroupC.I. The effect of vitamin B6 on cognition.Cochrane Database Syst. Rev.200320104CD004393 14584010
     [Google Scholar]
  24. DanielskiL.G. GiustinaA.D. GoldimM.P. FlorentinoD. MathiasK. GarbossaL. de Bona SchraiberR. LaurentinoA.O.M. GoulartM. MichelsM. de QueirozK.B. KohlhofM. RezinG.T. FortunatoJ.J. QuevedoJ. BarichelloT. Dal-PizzolF. CoimbraR.S. PetronilhoF. 6 reduces neurochemical and long-term cognitive alterations after Polymicrobial Sepsis: Involvement of the kynurenine pathway modulation.Mol. Neurobiol.20185565255526810.1007/s12035‑017‑0706‑0 28879460
     [Google Scholar]
  25. PerryT. HollowayH.W. WeerasuriyaA. MoutonP.R. DuffyK. MattisonJ.A. GreigN.H. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy.Exp. Neurol.2007203229330110.1016/j.expneurol.2006.09.028 17125767
     [Google Scholar]
  26. FrancoC.N. SeabrookL.J. NguyenS.T. LeonardJ.T. AlbrechtL.V. Simplifying the B complex: How vitamins B6 and B9 modulate one carbon metabolism in cancer and beyond.Metabolites2022121096110.3390/metabo12100961 36295863
     [Google Scholar]
  27. CurdtN. SchmittF.W. BouterC. IseniT. WeileH.C. AltunokB. BeindorffN. BayerT.A. CookeM.B. BouterY. Search strategy analysis of Tg4-42 Alzheimer Mice in the Morris Water Maze reveals early spatial navigation deficits.Sci. Rep.2022121545110.1038/s41598‑022‑09270‑1 35361814
     [Google Scholar]
  28. KraeuterA.K. GuestP.C. SarnyaiZ. The Y-maze for assessment of spatial working and reference memory in mice.Methods Mol. Biol.20191916105111
     [Google Scholar]
  29. MuraliM. ShivanandappaT. Endosulfan causes oxidative stress in the liver and brain that involves inhibition of NADH dehydrogenase and altered antioxidant enzyme status in rat.Ecotoxicol. Environ. Saf.202223911359310.1016/j.ecoenv.2022.113593 35567928
     [Google Scholar]
  30. IskusnykhI.Y. ZakharovaA.A. PathakD. Glutathione in brain disorders and aging.Molecules202227132410.3390/molecules27010324 35011559
     [Google Scholar]
  31. ThiendedsakulP. SantativongchaiP. BoonsoongnernP. YodsheewanR. TulayakulP. Glutathione-S-transferase activity in various organs of Crocodylus siamensis and its attenuation role in aflatoxin B1-induced cell apoptosis in human hepatocarcinoma cells.Vet. World2022151465410.14202/vetworld.2022.46‑54 35369592
     [Google Scholar]
  32. AliF. ManzoorU. BhattacharyaR. BansalA.K. ChandrashekharaiahK.S. SinghL.R. SaraswatiS.M. UverskyV. DarT.A. Brain metabolite, myo-inositol, inhibits catalase activity: A mechanism of the distortion of the antioxidant defense system in Alzheimer’s disease.ACS Omega2022715126901270010.1021/acsomega.1c06990 35474814
     [Google Scholar]
  33. BermanH.M. WestbrookJ. FengZ. GillilandG. BhatT.N. WeissigH. ShindyalovI.N. BourneP.E. The protein data bank.Nucleic Acids Res.200028123524210.1093/nar/28.1.235 10592235
     [Google Scholar]
  34. PettersenE.F. GoddardT.D. HuangC.C. CouchG.S. GreenblattD.M. MengE.C. FerrinT.E. UCSF Chimera—A visualization system for exploratory research and analysis.J. Comput. Chem.200425131605161210.1002/jcc.20084 15264254
     [Google Scholar]
  35. GuexN. PeitschM.C. SWISS-MODEL and the swiss-PdbViewer: An environment for comparative protein modeling.Electrophoresis1997181527142723
     [Google Scholar]
  36. TrottO. OlsonA.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem.201031245546110.1002/jcc.21334 19499576
     [Google Scholar]
  37. DeLanoW.L. Pymol: An open-source molecular graphics tool. CCP4 Newsl.Protein Crystallogr20024018292
     [Google Scholar]
  38. ShahabM. KhanS.S. ZulfatM. Bin JardanY.A. MekonnenA.B. BourhiaM. ZhengG. In silico mutagenesis-based designing of oncogenic SHP2 peptide to inhibit cancer progression.Sci. Rep.20231311008810.1038/s41598‑023‑37020‑4 37344519
     [Google Scholar]
  39. Al-MadhagiH.A. ShahabM. Finding consensus miRNAs silencing KLF1 expression as a promising therapeutic option of sickle cell anemia.Inform. Med. Unlocked20233910127210.1016/j.imu.2023.101272
     [Google Scholar]
  40. Salomon-FerrerR. GötzA.W. PooleD. Le GrandS. WalkerR.C. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh Ewald.J. Chem. Theory Comput.2013993878388810.1021/ct400314y 26592383
     [Google Scholar]
  41. RoeD.R. CheathamT.E. III PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data.J. Chem. Theory Comput.2013973084309510.1021/ct400341p 26583988
     [Google Scholar]
  42. GurerH. ErcalN. Can antioxidants be beneficial in the treatment of lead poisoning?Free Radic. Biol. Med.2000291092794510.1016/S0891‑5849(00)00413‑5 11084283
     [Google Scholar]
  43. PanJ. HuangX. LiY. LiM. YaoN. ZhouZ. LiX. Zinc protects against cadmium-induced toxicity by regulating oxidative stress, ions homeostasis and protein synthesis.Chemosphere201718826527310.1016/j.chemosphere.2017.08.106 28886561
     [Google Scholar]
  44. BourreJ-M. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: Micronutrients.J. Nutr. Health Aging2006105377385 17066209
     [Google Scholar]
  45. NasirA. KhanM. NoreenS. Ur RahmanM. ZahidM. ShahS.A. NabiG. Vitamin B1 via Nrf-2/TLR4 signaling pathway ameliorates scopolamine-induced memory dysfunction in adult mice.Arab. J. Chem.202417110535010.1016/j.arabjc.2023.105350
     [Google Scholar]
  46. Duc NguyenH. Hee JoW. HongM.H.N. KimM.S. Anti-inflammatory effects of B vitamins protect against tau hyperphosphorylation and cognitive impairment induced by 1,2 diacetyl benzene: An in vitro and in silico study.Int. Immunopharmacol.202210810873610.1016/j.intimp.2022.108736 35364429
     [Google Scholar]
  47. XuH. WangS. GaoF. LiC. Vitamin B6, B9, and B12 intakes and cognitive performance in elders: National health and nutrition examination survey, 2011–2014.Neuropsychiatr. Dis. Treat.20221853755310.2147/NDT.S337617 35359912
     [Google Scholar]
  48. LiuZ. LiP. ZhaoZ.H. ZhangY. MaZ.M. WangS.X. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in apoe −/− mice fed with high-fat diet.J. Diabetes Res.201620161748065
     [Google Scholar]
  49. LalK.J. DakshinamurtiK. ThliverisJ. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension.J. Hypertens.199614335536310.1097/00004872‑199603000‑00013 8723990
     [Google Scholar]
  50. El-kottA.F. Abd-LateifA.E.K.M. KhalifaH.S. MorsyK. IbrahimE.H. Bin-JumahM. Abdel-DaimM.M. AleyaL. Kaempferol protects against cadmium chloride-induced hippocampal damage and memory deficits by activation of silent information regulator 1 and inhibition of poly (ADP-Ribose) polymerase-1.Sci. Total Environ.202072813883210.1016/j.scitotenv.2020.138832 32353801
     [Google Scholar]
  51. RenuK. ChakrabortyR. MyakalaH. KotiR. FamurewaA.C. MadhyasthaH. VellingiriB. GeorgeA. ValsalaG.A. Molecular mechanism of heavy metals (Lead, Chromium, Arsenic, Mercury, Nickel and Cadmium) - induced hepatotoxicity - A review.Chemosphere202127112973510.1016/j.chemosphere.2021.129735 33736223
     [Google Scholar]
  52. AfridiH.I. KaziT.G. KaziN. JamaliM.K. ArainM.B. JalbaniN. BaigJ.A. SarfrazR.A. Evaluation of status of toxic metals in biological samples of diabetes mellitus patients.Diabetes Res. Clin. Pract.200880228028810.1016/j.diabres.2007.12.021 18276029
     [Google Scholar]
  53. BarichelloT. GenerosoJ.S. SimõesL.R. CerettaR.A. DominguiniD. FerrariP. GubertC. JornadaL.K. BudniJ. KapczinskiF. QuevedoJ. Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.Exp. Biol. Med.2014239101360136510.1177/1535370214535896 24903161
     [Google Scholar]
  54. CalabreseV. CorneliusC. Dinkova-KostovaA.T. CalabreseE.J. MattsonM.P. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders.Antioxid. Redox Signal.201013111763181110.1089/ars.2009.3074 20446769
     [Google Scholar]
  55. CalabreseV. MancusoC. CalvaniM. RizzarelliE. ButterfieldD.A. GiuffridaS.A.M. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity.Nat. Rev. Neurosci.200781076677510.1038/nrn2214 17882254
     [Google Scholar]
  56. CalabreseE.J. IavicoliI. CalabreseV. Hormesis: Why it is important to biogerontologists.Biogerontology201213321523510.1007/s10522‑012‑9374‑7 22270337
     [Google Scholar]
/content/journals/cn/10.2174/1570159X22999240730154422
Loading
Vitamin B6 Via p-JNK/Nrf-2/NF-κB Signaling Ameliorates Cadmium Chloride-Induced Oxidative Stress Mediated Memory Deficits in Mice Hippocampus
Curr. Neuropharmacol. 23, 116 (2025); https://doi.org/10.2174/1570159X22999240730154422
/content/journals/cn/10.2174/1570159X22999240730154422
/content/journals/cn/10.2174/1570159X22999240730154422
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Alzheimer's disease; anti-inflammatory; neurodegenerative disease; neuroinflammation; neurotoxicity; Oxidative stress

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test