Skip to main content
SpringerLink
Log in

Kolaviron via anti-inflammatory and redox regulatory mechanisms abates multi-walled carbon nanotubes-induced neurobehavioral deficits in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

A Correction to this article was published on 27 January 2020

This article has been updated

Abstract

Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochemical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p < 0.05) enhanced the locomotor, motor, and exploratory activities namely total distance traveled, maximum speed, total time mobile, mobile episode, path efficiency, body rotation, absolute turn angle, and negative geotaxis when compared with rats exposed to MWCNTs alone. Further, kolaviron markedly abated the decrease in the acetylcholinesterase activity and antioxidant defense system as well as the increase in oxidative stress and inflammatory biomarkers induced by MWCNT exposure in the cerebrum, cerebellum, and mid-brain of rats. The amelioration of MWCNT-induced neuronal degeneration in the brain structures by kolaviron was verified by histological and morphometrical analyses. Taken together, kolaviron abated MWCNT-induced neurotoxicity via anti-inflammatory and redox regulatory mechanisms.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14

Similar content being viewed by others

Change history

  • 27 January 2020

    After publication of this paper, the authors discovered that the name of the first author, Isaac Adegboyega Adedara, was missing in the proof. Dr. Adedara’s intellectual contributions to the present article include conception and design of the study, manuscript writing and approval of the final version of the manuscript.

References

  • Abarikwu SO (2014) Kolaviron, a natural flavonoid from the seeds of Garcinia kola, reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion, and inflammatory transcription factors, ERK1/2, NF-κB, p38, Akt, p-c-JUN and JNK. Biochim Biophys Acta 1840(7):2373–2381

    CAS  PubMed  Google Scholar 

  • Abu Gazia M, El-Magd MA (2019) Effect of pristine and functionalized multiwalled carbon nanotubes on rat renal cortex. Acta Histochem 121(2):207–217

    CAS  PubMed  Google Scholar 

  • Adedara IA, Abolaji AO, Rocha JB, Farombi EO (2016a) Diphenyl diselenide protects against mortality, locomotor deficits and oxidative stress in Drosophila melanogaster model of manganese-induced neurotoxicity. Neurochem Res 41:1430–1438

    CAS  PubMed  Google Scholar 

  • Adedara IA, Rosemberg DB, de Souza D, Farombi EO, Aschner M, Souza DO, Rocha JBT (2016b) Neurobehavioral and biochemical changes in Nauphoeta cinerea following dietary exposure to chlorpyrifos. Pestic Biochem Physiol 130:22–30

    CAS  PubMed  Google Scholar 

  • Adedara IA, Abolaji AO, Idris UF, Olabiyi BF, Onibiyo EM, Ojuade TD, Farombi EO (2017) Neuroprotective influence of taurine on fluoride-induced biochemical and behavioral deficits in rats. Chem Biol Interact 261:1–10

    CAS  PubMed  Google Scholar 

  • Adedara IA, Anao OO, Forcados GE, Awogbindin IO, Agbowo A, Ola-Davies OE, Patlolla AK, Tchounwou PB, Farombi EO (2018) Low doses of multi-walled carbon nanotubes elicit hepatotoxicity in rats with markers of oxidative stress and induction of pro-inflammatory cytokines. Biochem Biophys Res Commun 503(4):3167–3173

    CAS  PubMed  Google Scholar 

  • Akinmoladun AC, Akinrinola BL, Olaleye MT, Farombi EO (2015) Kolaviron, a Garcinia kola biflavonoid complex, protects against ischemia/reperfusion injury: pertinent mechanistic insights from biochemical and physical evaluations in rat brain. Neurochem Res 40(4):777–787

    CAS  PubMed  Google Scholar 

  • Antúnez-Flores W, Valenzuela-Muñiz AM, Amézaga-Madrid P, Alonso-Nuñez G, Verde Y, Martínez-Sánchez R, Miki-Yoshida M (2008) Simplified route to multi-walled carbon nanotube synthesis by aerosol assisted chemical vapor deposition. J Nanosci Nanotechnol 8(12):6451–6455

    PubMed  Google Scholar 

  • Aratani Y (2018) Myeloperoxidase: its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys 640:47–52

    CAS  PubMed  Google Scholar 

  • Aschberger K, Johnston HJ, Stone V, Aitken RJ, Hankin SM, Peters SA, Tran CL, Christensen FM (2010) Review of carbon nanotubes toxicity and exposure--appraisal of human health risk assessment based on open literature. Crit Rev Toxicol 40(9):759–790

    CAS  PubMed  Google Scholar 

  • Bancroft JD, Gamble M (2008) Theory and practice of histology techniques, 6th edn. Churchill Livingstone Elsevier, Philadelphia (PA), pp 83–134

    Google Scholar 

  • Baud V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11(9):372–377

    CAS  PubMed  Google Scholar 

  • Belyanskaya L, Weigel S, Hirsch C, Tobler U, Krug HF, Wick P (2009) Effects of carbon nanotubes on primary neurons and glial cells. Neurotoxicology 30:702–711

    CAS  PubMed  Google Scholar 

  • Bianco A, Kostarelos K, Partidos CD, Prato M (2005) Biomedical applications of functionalised carbon nanotubes. Chem Commun 7:571–577

    Google Scholar 

  • Bradford MM (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    CAS  PubMed  Google Scholar 

  • Brunauer S, Emmett PH, Teller E (1938) Adsorption of gases in multi-molecular layers. J Am Chem Soc 60:309–319

    CAS  Google Scholar 

  • Chen T, Yang J, Ren G, Yang Z, Zhang T (2013) Multi-walled carbon nanotube increases the excitability of hippocampal CA1 neurons through inhibition of potassium channels in rat's brain slices. Toxicol Lett 217:121–128

    CAS  PubMed  Google Scholar 

  • Chen T, Yang J, Zhang H, Ren G, Yang Z, Zhang T (2014) Multi-walled carbon nanotube inhibits CA1 glutamatergic synaptic transmission in rat's hippocampal slices. Toxicol Lett 229:423–429

    CAS  PubMed  Google Scholar 

  • Claiborne A (1995) Catalase activity. In: Greewald AR (ed) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 237–242

    Google Scholar 

  • Day J, Damsma G, Fibiger HC (1991) Cholinergic activity in the rat hippocampus, cortex and striatum correlates with locomotor activity: an in vivo microdialysis study. Pharmacol Biochem Behav 38:723–729

    CAS  PubMed  Google Scholar 

  • De Marchi L, Neto V, Pretti C, Figueira E, Chiellini F, Morelli A, Soares AMVM, Freitas R (2018) Toxic effects of multi-walled carbon nanotubes on bivalves: comparison between functionalized and non-functionalized nanoparticles. Sci Total Environ 622-623:1532–1542

    PubMed  Google Scholar 

  • Dong J, Ma Q (2016) Suppression of basal and carbon nanotube-induced oxidative stress, inflammation and fibrosis in mouse lungs by Nrf2. Nanotoxicology. 10(6):699–709

    CAS  PubMed  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    CAS  PubMed  Google Scholar 

  • Farombi EO, Nwaokeafor IA (2005) Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats. Clin Exp Pharmacol Physiol 32(8):667–674

    CAS  PubMed  Google Scholar 

  • Farombi EO, Tahnteng JG, Agboola AO, Nwankwo JO, Emerole GO (2000) Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron-a Garcinia kola seed extract. Food Chem Toxicol 38:535–541

    CAS  PubMed  Google Scholar 

  • Farombi EO, Adedara IA, Forcados GE, Anao OO, Agbowo A, Patlolla AK (2016) Responses of testis, epididymis, and sperm of pubertal rats exposed to functionalized multiwalled carbon nanotubes. Environ Toxicol 31:543–551

    CAS  PubMed  Google Scholar 

  • Farombi EO, Awogbindin IO, Farombi TH, Oladele JO, Izomoh ER, Aladelokun OB, Ezekiel IO, Adebambo OI, Abah VO (2019) Neuroprotective role of kolaviron in striatal redo-inflammation associated with rotenone model of Parkinson's disease. Neurotoxicology 73:132–141

    CAS  PubMed  Google Scholar 

  • Gao J, Zhang X, Yu M, Ren G, Yang Z (2015) Cognitive deficits induced by multi-walled carbon nanotubes via the autophagic pathway. Toxicology 337:21–29

    CAS  PubMed  Google Scholar 

  • Gorny JH, Gorny B, Wallace DG, Whishaw IQ (2002) Fimbria-fornix lesions disrupt the dead reckoning (homing) component of exploratory behavior in mice. Learn Mem 9(6):387–394

    PubMed  PubMed Central  Google Scholar 

  • Granell S, Gironella M, Bulbena O, Panés J, Mauri M, Sabater L, Aparisi L, Gelpí E, Closa D (2003) Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis. Crit Care Med 31:525–530

    CAS  PubMed  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    CAS  PubMed  Google Scholar 

  • Grochowski C, Litak J, Kamieniak P, Maciejewski R (2018) Oxidative stress in cerebral small vessel disease. Role of reactive species. Free Radic Res 52(1):1–13

    CAS  PubMed  Google Scholar 

  • Guzik TJ, Korbut R, Adamek-Guzik T (2003) Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol 54:469–487

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Han YG, Xu J, Li ZG, Ren GG, Yang Z (2012) In vitro toxicity of multi-walled carbon nanotubes in C6 rat glioma cells. Neurotoxicology 33:1128–1134

    CAS  PubMed  Google Scholar 

  • Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology. 61:154–166

    CAS  PubMed  Google Scholar 

  • Ishola IO, Adamson FM, Adeyemi OO (2017) Ameliorative effect of kolaviron, a biflavonoid complex from Garcinia kola seeds against scopolamine-induced memory impairment in rats: role of antioxidant defense system. Metab Brain Dis 32(1):235–245

    CAS  PubMed  Google Scholar 

  • Iwu MM (1985) Antihepatoxic constituents of Garcinia kola seeds. Experientia 41(5):699–700

    CAS  PubMed  Google Scholar 

  • Jacobs CB, Peairs MJ, Venton BJ (2010) Review: carbon nanotube based electrochemical sensors for biomolecules. Anal Chim Acta 662:105–127

    CAS  PubMed  Google Scholar 

  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4 bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169

    CAS  PubMed  Google Scholar 

  • Kamran U, Heo YJ, Lee JW, Park SJ (2019) Functionalized carbon materials for electronic devices: a review. Micromachines (Basel) 10(4). https://doi.org/10.3390/mi10040234

  • Kumar R, Dhanawat M, Kumar S, Singh BN, Pandit JK, Sinha VR (2014) Carbon nanotubes: a potential concept for drug delivery applications. Rec Patents Drug Deliv Formulat 8:12–26

    CAS  Google Scholar 

  • Lin Y, Taylor S, Li H, Shiral Fernando KA, Qu L, Wang W, Gu L, Zhou B, Ping Sun Y (2004) Advances toward bioapplications of carbon nanotubes. J Mater Chem 14:527–541

    CAS  Google Scholar 

  • Malarkey EB, Parpura V (2007) Applications of carbon nanotubes in neurobiology. Neurodegener Dis 4(4):292–299

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Motz BA, Alberts JR (2005) The validity and utility of geotaxis in young rodents. Neurotoxicol Teratol 27(4):529–533

    CAS  PubMed  Google Scholar 

  • Ndrepepa G (2019) Myeloperoxidase - a bridge linking inflammation and oxidative stress with cardiovascular disease. Clin Chim Acta 493:36–51

    CAS  PubMed  Google Scholar 

  • Nel AE (2013) Implementation of alternative test strategies for the safety assessment of engineered nanomaterials. J Intern Med 274(6):561–577

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nwankwo JO, Tahnteng JG, Emerole GO (2000) Inhibition of aflatoxin B1 genotoxicity in human liver-derived HepG2 cells by kolaviron biflavonoids and molecular mechanisms of action. Eur J Cancer Prev 9(5):351–361

    CAS  PubMed  Google Scholar 

  • Ojo OB, Amoo ZA, Saliu IO, Olaleye MT, Farombi EO, Akinmoladun AC (2019) Neurotherapeutic potential of kolaviron on neurotransmitter dysregulation, excitotoxicity, mitochondrial electron transport chain dysfunction and redox imbalance in 2-VO brain ischemia/reperfusion injury. Biomed Pharmacother 111:859–872

    CAS  PubMed  Google Scholar 

  • Olajide OJ, Asogwa NT, Moses BO, Oyegbola CB (2017) Multidirectional inhibition of cortico-hippocampal neurodegeneration by kolaviron treatment in rats. Metab Brain Dis 32(4):1147–1161

    CAS  PubMed  Google Scholar 

  • Onasanwo SA, Rotu RA (2016) Antinociceptive and anti-inflammatory potentials of kolaviron: mechanisms of action. J Basic Clin Physiol Pharmacol 27(4):363–370

    CAS  PubMed  Google Scholar 

  • Osuagwu FC, Owoeye O, Avwioro OG, Oluwadara OO, Imosemi IO, Ajani RS, Ogunleye AA, Oladejo OW (2007) Reduction of hippocampal CA 1 neurons in Wistar rats following the administration of phenytoin for seven days. Afr J Med Med Sci 36:103–108

    CAS  PubMed  Google Scholar 

  • Patlolla AK, Berry A, Tchounwou PB (2011) Study of hepatotoxicity and oxidative stress in male Swiss-Webster mice exposed to functionalized multi-walled carbon nanotubes. Mol Cell Biochem 358:189–199

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poprac P, Jomova K, Simunkova M, Kollar V, Rhodes CJ, Valko M (2017) Targeting free radicals in oxidative stress-related human diseases. Trends Pharmacol Sci 38(7):592–607

    CAS  PubMed  Google Scholar 

  • Reddy AR, Rao MV, Krishna DR, Himabindu V, Reddy YN (2011) Evaluation of oxidative stress and anti-oxidant status in rat serum following exposure of carbon nanotubes. Regul Toxicol Pharmacol 59(2):251–257

    CAS  PubMed  Google Scholar 

  • Riemann BL, Lephart SM (2002) The sensorimotor system, part I: the physiologic basis of functional joint stability. J Athl Train 37:71–79

    PubMed  PubMed Central  Google Scholar 

  • Rode A, Sharma S, Mishra DK (2018) Carbon nanotubes: classification, method of preparation and pharmaceutical application. Curr Drug Deliv 15(5):620–629

    CAS  PubMed  Google Scholar 

  • Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    CAS  PubMed  Google Scholar 

  • Shichiri M (2014) The role of lipid peroxidation in neurological disorders. J Clin Biochem Nutr 54(3):151–160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tsukahara T, Matsuda Y, Haniu H (2014) The role of autophagy as a mechanism of toxicity induced by multi-walled carbon nanotubes in human lung cells. Int J Mol Sci 16(1):40–48

    PubMed  PubMed Central  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84

    CAS  PubMed  Google Scholar 

  • Wang J, Schlagenhauf L, Setyan A (2017) Transformation of the released asbestos, carbon fibers and carbon nanotubes from composite materials and the changes of their potential health impacts. J Nanobiotechnol 15(1):15. https://doi.org/10.1186/s12951-017-0248-7

    Article  CAS  Google Scholar 

  • Zhao X, Chang S, Long J, Li J, Li X, Cao Y (2019) The toxicity of multi-walled carbon nanotubes (MWCNTs) to human endothelial cells: the influence of diameters of MWCNTs. Food Chem Toxicol 126:169–177

    CAS  PubMed  Google Scholar 

Download references

Funding

This research was supported in part by the National Institute of Health (NIH)-NIMHD with the grant number G12MD007581 and TETFUND National Research Fund (NRF) 2015 grant.

Author information

Authors and Affiliations

  1. Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Isaac A. Adedara, Ifeoluwa O. Awogbindin, Ikenna C. Maduako & Ebenezer O. Farombi

  2. Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Olatunde Owoeye

  3. Department of Anatomy, College of Medicine, Bowen University, Iwo, Nigeria

    Akinola O. Ajeleti

  4. Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Solomon E. Owumi

  5. College of Science Engineering and Technology, NIH-RCMI Center for Environmental Health, Jackson State University, Jackson, MS, USA

    Anita K. Patlolla

Authors
  1. Isaac A. Adedara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ifeoluwa O. Awogbindin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olatunde Owoeye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ikenna C. Maduako
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akinola O. Ajeleti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Solomon E. Owumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anita K. Patlolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ebenezer O. Farombi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ebenezer O. Farombi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

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

The original version of this article was revised: This article was originally published with the first author Isaac A. Adedara missing in the proof.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adedara, I.A., Awogbindin, I.O., Owoeye, O. et al. Kolaviron via anti-inflammatory and redox regulatory mechanisms abates multi-walled carbon nanotubes-induced neurobehavioral deficits in rats. Psychopharmacology 237, 1027–1040 (2020). https://doi.org/10.1007/s00213-019-05432-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-019-05432-8

Keywords

Search

Navigation