SpringerLink
Log in

Modulatory Role of Curcumin on Cobalt-Induced Memory Deficit, Hippocampal Oxidative Damage, Astrocytosis, and Nrf2 Expression

  • Research Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

A Correction to this article was published on 03 August 2023

This article has been updated

Abstract

Chemical overexposure is a growing environmental risk factor for many medical issues. Cobalt toxicity from environmental, industrial, and medical exposure has previously been linked to neurological impairment. Hence, the current study looked into the neuroprotective potential of curcumin, a natural polyphenol contained in the spice turmeric, against cobalt-induced neurotoxicity. Adult rats were randomly divided into six groups as follows: control, 40 mg/kg cobalt chloride (CoCl2) only, 240 mg/kg curcumin only, 120 mg/kg or 240 mg/kg curcumin, or 100 mg/kg vitamin C co-administered with CoCl2. The administration was via oral route daily for 4 weeks. After that, neurobehavioral tests were undertaken to evaluate short-term spatial memory. Biochemical investigation was performed to determine the hippocampal levels of status via measures of SOD, CAT, GST, and LPO. Furthermore, immunohistochemical assessment of the expression of GFAP and Nrf2 in the hippocampus was carried out. In the CoCl2 group, the results showed altered behavioral responses, a decrease in antioxidant activities, increased expression of GFAP and the number of activated astrocytes, and decreased immunoexpression of Nrf2. These effects were mitigated in the curcumin- and vitamin C–treated groups. These results collectively imply that curcumin enhances memory functions in rats exposed to cobalt possibly by attenuating oxidative responses, mitigating astrocytosis, and modulating Nrf2 signaling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Data and materials available on request.

Change history

References

  • Abad S, Camarasa J, Pubill D, Camins A, Escubedo E (2016) Adaptive plasticity in the hippocampus of young mice intermittently exposed to MDMA could be the origin of memory deficits. Mol Neurobiol 53(10):7271–7283

    Article  CAS  PubMed  Google Scholar 

  • Abubakar K, Muhammad Mailafiya M, Danmaigoro A, Musa Chiroma S, Abdul Rahim EB, Zakaria ZAB (2019) Curcumin attenuates lead-induced cerebellar toxicity in rats via chelating activity and inhibition of oxidative stress. Biomolecules 9(9):453

    Article  PubMed  PubMed Central  Google Scholar 

  • Ajayi AM, Chidebe EO, Ben-Azu B, Umukoro S (2020) Chrysophyllum albidum (African star apple) fruit-supplemented diet enhances cognitive functions and attenuates lipopolysaccharide-induced memory impairment, oxidative stress, and release of proinflammatory cytokines. Nutrire 45(2):1–13

    Article  Google Scholar 

  • Ajibade A, Ogunmola I, Okeleye A (2021) Ameliorative effects of Moringa oleifera leaf extract on the cobalt chloride-induced liver damage in adult wistar rats. Sys Rev Pharm 12(12):3865–3871

    CAS  Google Scholar 

  • Ajibade TO, Oyagbemi AA, Omobowale TO, Asenuga ER, Adigun KO (2017) Quercetin and vitamin C mitigate cobalt chloride-induced hypertension through reduction in oxidative stress and nuclear factor kappa beta (NF-Kb) expression in experimental rat model. Biol Trace Elem Res 175(2):347–359

    Article  CAS  PubMed  Google Scholar 

  • Akingbade GT, Ijomone OM, Imam A, Aschner M, Ajao MS (2021) d-Ribose-l-cysteine improves glutathione levels, neuronal and mitochondrial ultrastructural damage, caspase-3 and GFAP expressions following manganese-induced neurotoxicity. Neurotox Res 39(6):1846–1858

    Article  CAS  PubMed  Google Scholar 

  • Akinrinde A, Adebiyi O (2019) Neuroprotection by luteolin and gallic acid against cobalt chloride-induced behavioural, morphological and neurochemical alterations in Wistar rats. Neurotoxicology 74:252–263

    Article  CAS  PubMed  Google Scholar 

  • Albus U (2012) Guide for the care and use of laboratory animals, 8th edn. London, England, SAGE Publications Sage UK

    Google Scholar 

  • Bardak H, Uğuz AC, Bardak Y (2018) Protective effects of melatonin and memantine in human retinal pigment epithelium (ARPE-19) cells against 2-ethylpyridine-induced oxidative stress: implications for age-related macular degeneration. Cutan Ocul Toxicol 37(2):112–120

    Article  CAS  PubMed  Google Scholar 

  • Burdette D, Olivarez M, Waris G (2010) Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway: THIS ARTICLE HAS BEEN RETRACTED. J Gen Virol 91(3):681–690

    Article  CAS  PubMed  Google Scholar 

  • Chang HC, Chen H-W, Tung H-S, Liu K-L, Tsai C-W, Lii C-K (2010) Butein up-regulates the expression of the π class of glutathione S-transferase in rat primary hepatocytes through the ERK/AP-1 pathway. J Agric Food Chem 58(16):8994–9000

    Article  CAS  PubMed  Google Scholar 

  • Claiborne A (1985) Handbook of methods for oxygen radical research. Florida: CRC Press, Boca Raton:283–284

  • de Sousa Macedo LLB, Antunes FTT, de Andrade Alvarenga W, Batista MCC, de Moura MSB, Farias MNL, Caminski ES, Dallegrave E, Grivicich I, de Souza AH (2022) Curcumin for attention-deficit–hyperactivity disorder: a systematic review and preliminary behavioral investigation. Naunyn-Schmiedeberg’s Arch Pharmacol:1–11

  • Dong W, Yang B, Wang L, Li B, Guo X, Zhang M, Jiang Z, Fu J, Pi J, Guan D (2018) Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling. Toxicol Appl Pharmacol 346:28–36

    Article  CAS  PubMed  Google Scholar 

  • Ebokaiwe AP, Ijomone OM, Osawe SO, Osuji O, Alo M (2019) Influence of Loranthus micranthus against STZ-induced neurobehavioral deficits in diabetic rats. Neurochem J 13(3):283–294

    Article  CAS  Google Scholar 

  • Ebokaiwe AP, Obeten KE, Okori SO, David EE, Olusanya O, Chukwu CJ, Okoro N, Ehiri RC (2020) Co-administration of selenium nanoparticles and metformin abrogate testicular oxidative injury by suppressing redox imbalance, augmenting sperm quality and Nrf2 protein expression in streptozotocin-induced diabetic rats. Biol Trace Elem Res 198(2):544–556

    Article  CAS  PubMed  Google Scholar 

  • Erukainure OL, Ijomone OM, Sanni O, Aschner M, Islam M (2019) Type 2 diabetes induced oxidative brain injury involves altered cerebellar neuronal integrity and elemental distribution, and exacerbated Nrf2 expression: therapeutic potential of raffia palm (Raphia hookeri) wine. Metab Brain Dis 34(5):1385–1399

    Article  CAS  PubMed  Google Scholar 

  • Farombi E, Tahnteng J, Agboola A, Nwankwo J, Emerole G (2000) Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron—a Garcinia kola seed extract. Food Chem Toxicol 38(6):535–541

    Article  CAS  PubMed  Google Scholar 

  • Fedosova E, Shatskova A, Sarkisova KY (2021) Ethosuximide increases exploratory motivation and improves episodic memory in the novel object recognition test in WAG/Rij rats with genetic absence epilepsy. Neurosci Behav Physiol 51(4):501–512

    Article  CAS  Google Scholar 

  • Ghosh S, Banerjee S, Sil PC (2015) The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: a recent update. Food Chem Toxicol 83:111–124

    Article  CAS  PubMed  Google Scholar 

  • Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Z, Tang J, Wang J, Zheng F, Zhang C, Wang Y-L, Cai P, Shao W, Yu G, Wu S (2021) The negative role of histone acetylation in cobalt chloride-induced neurodegenerative damages in SHSY5Y cells. Ecotoxicol Environ Saf 209:111832

    Article  CAS  PubMed  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139

    Article  CAS  PubMed  Google Scholar 

  • Han Y, Chen R, Lin Q, Liu Y, Ge W, Cao H, Li J (2021) Curcumin improves memory deficits by inhibiting HMGB1-RAGE/TLR4-NF-κB signalling pathway in APPswe/PS1dE9 transgenic mice hippocampus. J Cell Mol Med 25(18):8947–8956. https://doi.org/10.1111/jcmm.16855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hewlings SJ, Kalman DS (2017) Curcumin: a review of its effects on human health. Foods 6(10):92

    Article  PubMed  PubMed Central  Google Scholar 

  • IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2006) Cobalt in hard metals and cobalt sulfate, gallium arsenide, indium phosphide and vanadium pentoxide. IARC Monogr Eval Carcinog Risks Hum 86:1

    PubMed Central  Google Scholar 

  • Ijomone OM, Olatunji SY, Owolabi JO, Naicker T, Aschner M (2018) Nickel-induced neurodegeneration in the hippocampus, striatum and cortex; an ultrastructural insight, and the role of caspase-3 and α-synuclein. J Trace Elem Med Biol 50:16–23

    Article  CAS  PubMed  Google Scholar 

  • Kahuripour M, Behroozi Z, Rahimi B, Hamblin MR, Ramezani F (2022) The potential of curcumin for treating spinal cord injury: a meta-analysis study. Nutr Neurosc:1–12

  • Liu M, Liu P, Zheng B, Liu Y, Li L, Han X, Liu Y, Chu L (2022) Cardioprotective effects of alantolactone on isoproterenol-induced cardiac injury and cobalt chloride-induced cardiomyocyte injury. Int J Immunopathol Pharmacol 36:20587384211051990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu W, Tong J, Zhou M, Wen J (2022) The total flavones of Abelmoschus manihot inhibit reactive proliferation of astrocytes following cerebral ischemia. Pharmacogn Mag 18(79):752

    CAS  Google Scholar 

  • Martinez C-A, Kerr B, ** C, Cistulli PA, Cook KM (2019) Obstructive sleep apnea activates HIF-1 in a hypoxia dose-dependent manner in HCT116 colorectal carcinoma cells. Int J Mol Sci 20(2):445

    Article  PubMed  PubMed Central  Google Scholar 

  • Mary CPV, Vijayakumar S, Shankar R (2018) Metal chelating ability and antioxidant properties of curcumin-metal complexes–a DFT approach. J Mol Graph Model 79:1–14

    Article  CAS  PubMed  Google Scholar 

  • Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175

    Article  CAS  PubMed  Google Scholar 

  • Mohamed AA-R, Metwally MM, Khalil SR, Salem GA, Ali HA (2019) Moringa oleifera extract attenuates the CoCl2 induced hypoxia of rat’s brain: expression pattern of HIF-1α, NF-kB, MAO and EPO. Biomed Pharmacother 109:1688–1697

    Article  Google Scholar 

  • Oria R, Obeten K, Etetim A, Mgbolu P, Ikoku G, Ijomone O (2022) Ameliorative effect of Prosopis africana seed extract on cobalt chloride induced cerebellar toxicity: neurobehavioural, histomorphological and biochemical findings. Niger J Neurosci 13(1):9–19

    Article  Google Scholar 

  • Packer M (2016) Cobalt cardiomyopathy: a critical reappraisal in light of a recent resurgence. Circ Heart Fail 9(12):e003604

    Article  PubMed  Google Scholar 

  • Park S-I, Lee EH, Kim SR, Jang YP (2017) Anti-apoptotic effects of Curcuma longa L. extract and its curcuminoids against blue light-induced cytotoxicity in A2E-laden human retinal pigment epithelial cells. J Pharm Pharmacol 69(3):334–340

    Article  CAS  PubMed  Google Scholar 

  • Potteti HR, Noone PM, Tamatam CR, Ankireddy A, Noel S, Rabb H, Reddy SP (2021) Nrf2 mediates hypoxia-inducible HIF1α activation in kidney tubular epithelial cells. Am J Physiol-Ren Physiol 320(3):F464–F474

    Article  CAS  Google Scholar 

  • Prieur EA, Jadavji NM (2019) Assessing spatial working memory using the spontaneous alternation Y-maze test in aged male mice. Bio-Protoc 9(3):e3162–e3162

    Article  PubMed  PubMed Central  Google Scholar 

  • Ramírez-Mendoza AA, Ramírez-Herrera MA, Cortez-Álvarez CR, Nery-Flores SD, Tejeda-Martínez AR, Romero-Prado MMdJ, Mendoza-Magaña ML (2022) Curcumin modifies the activity of plasmatic antioxidant enzymes and the hippocampal oxidative profile in rats upon acute and chronic exposure to ozone. Molecules 27(14):4531

    Article  PubMed  PubMed Central  Google Scholar 

  • Rao SS, Lago L, Volitakis I, Shukla JJ, McColl G, Finkelstein DI, Adlard PA (2021) Deferiprone treatment in aged transgenic tau mice improves Y-maze performance and alters tau pathology. Neurotherapeutics 18(2):1081–1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santana-Martínez RA, Silva-Islas CA, Fernández-Orihuela YY, Barrera-Oviedo D, Pedraza-Chaverri J, Hernández-Pando R, Maldonado PD (2019) The therapeutic effect of curcumin in quinolinic acid-induced neurotoxicity in rats is associated with BDNF, ERK1/2, Nrf2, and antioxidant enzymes. Antioxidants 8(9):388

    Article  PubMed  PubMed Central  Google Scholar 

  • Scharf B, Clement CC, Zolla V, Perino G, Yan B, Elci SG, Purdue E, Goldring S, Macaluso F, Cobelli N (2014) Molecular analysis of chromium and cobalt-related toxicity. Sci Rep 4(1):1–12

    Article  Google Scholar 

  • Shedd K (2015) Minerals yearbook: cobalt. US Geological Survey

  • Tang J, Li Y, Liu X, Yu G, Zheng F, Guo Z, Zhang Y, Shao W, Wu S, Li H (2022) Cobalt induces neurodegenerative damages through impairing autophagic flux by activating hypoxia-inducible factor-1α triggered ROS overproduction. Sci Total Environ:159432

  • Taylor CM, Golding J, Emond AM (2014) Lead, cadmium and mercury levels in pregnancy: the need for international consensus on levels of concern. J Dev Orig Health Dis 5(1):16–30

    Article  CAS  PubMed  Google Scholar 

  • Tuominen VJ, Ruotoistenmäki S, Viitanen A, Jumppanen M, Isola J (2010) ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Breast Cancer Res 12(4):1–12

    Article  Google Scholar 

  • Wang X, He Y, Tian J, Muhammad I, Liu M, Wu C, Xu C, Zhang X (2021) Ferulic acid prevents aflatoxin B1-induced liver injury in rats via inhibiting cytochrome P450 enzyme, activating Nrf2/GST pathway and regulating mitochondrial pathway. Ecotoxicol Environ Saf 224:112624

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Liu F, Liu M, Zhou X, Wang M, Cao K, ** S, Shan A, Feng X (2022) Curcumin mitigates aflatoxin B1-induced liver injury via regulating the NLRP3 inflammasome and Nrf2 signaling pathway. Food Chem Toxicol 161:112823

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Zhao J, Bai Z, Luo L, Wu F, Li B, Shan Y (2021) Sulforaphane inhibits the production of Aβ partially through the activation of Nrf2-regulated oxidative stress. Food Funct 12(22):11482–11490

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Tertiary Education Fund (Tetfund) Institution-Based Research (IBR) to Rademene S. Oria. Omamuyovwi M. Ijomone is supported by the International Brain Research Organization (IBRO) and International Society of Neurochemistry (ISN).

Funding

This work was funded by Tertiary Education Trust Fund (TETF/DR&D/CE/UNI/CALABAR/IBR/2019/VOL.1).

Author information

Authors and Affiliations

  1. Department of Anatomy, College of Medicine, Faculty of Basic Medical Sciences, University of Nigeria, Nsukka, Enugu Campus, Nsukka, Nigeria

    Rademene S. Oria, Godson E. Anyanwu, Emmanuel A. Esom, Johnson N. Nto, Amechi U. Katchy & Augustine U. Agu

  2. Department of Human Anatomy, Faculty of Basic Medical Sciences, Cross River University of Technology (CRUTECH), Okuku Campus, Okuku, Cross River, Nigeria

    Rademene S. Oria

  3. The Neuro-Lab, School of Basic Medical Sciences, Federal University of Technology, Akure, Nigeria

    Omamuyovwi M. Ijomone

  4. Department of Human Anatomy, School of Basic Medical Sciences, Federal University of Technology, Akure, Nigeria

    Omamuyovwi M. Ijomone

Authors
  1. Rademene S. Oria
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Godson E. Anyanwu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emmanuel A. Esom
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johnson N. Nto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amechi U. Katchy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Augustine U. Agu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Omamuyovwi M. Ijomone
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The study design and conceptualization were performed by Rademene S. Oria and Godson E. Anyanwu. Material preparation, data collection, and analysis were performed by Emmanuel A. Esom, Johnson N. Nto, Amechi U. Katchy, and Augustine U. Agu. The first draft of the manuscript was written by Rademene S. Oria and supervised by Godson E. Anyanwu. Data analysis, interpretation, and critical revision of manuscript were done by Omamuyovwi M. Ijomone. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Godson E. Anyanwu.

Ethics declarations

Ethical Considerations

All animals were treated strictly following the National Institute of Health’s recommendations in the guide for the care and use of laboratory animals (Albus 2012).

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oria, R.S., Anyanwu, G.E., Esom, E.A. et al. Modulatory Role of Curcumin on Cobalt-Induced Memory Deficit, Hippocampal Oxidative Damage, Astrocytosis, and Nrf2 Expression. Neurotox Res 41, 201–211 (2023). https://doi.org/10.1007/s12640-023-00635-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-023-00635-6

Keywords

Search

Navigation