Skip to main content

Advertisement

SpringerLink
Log in

Rutin alleviates cadmium-induced neurotoxicity in Wistar rats: involvement of modulation of nucleotide-degrading enzymes and monoamine oxidase

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Rutin is a flavonoid commonly found in many vegetables, fruits and other plant species. Thus, this study investigated the protective role of rutin on cognitive function and impairment of ectonucleotidase, monoamine oxidase (MAO) and antioxidant enzymes activities in the cortex and hippocampus of cadmium-induced rats. Cognitive impairment was induced by an oral administration of 5 mg/kg Cadmium chloride for 14 consecutive days. Rutin was dissolved in 2% dimethyl sulfoxide (DMSO) and administered orally at the doses of 25 and 50 mg/kg for 14 days. Thereafter, animals were divided into six groups (n = 6) as follows: control, rutin 25 mg/kg, rutin 50 mg/kg, cadmium, cadmium plus rutin 25 mg/kg, cadmium plus rutin 50 mg/kg. After treatment period of 14 days, animals were sacrificed and the brain was dissected into cortex and hippocampus. Results showed that cadmium caused a significant increase in ectonucleotidases, adenosine deaminase (ADA) and MAO activities, with a concomitant decrease in thiol levels and antioxidant enzymes activities. However, treatment with rutin decreased ectonucleotidase, ADA and MAO activities in cadmium-induced rats. In addition, rutin reduced residual level of cadmium ion in the brain of cadmium-induced rats. Conclusively, present findings revealed that rutin could prevent/restored the impairment of the enzymes that regulate the purinergic and monoaminergic extracellular signaling and restore antioxidant status in cognitive impairment caused by prolonged cadmium exposure.

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

Similar content being viewed by others

References

  • Ablat N, Lv D, Ren R, Xiaokaiti Y, Ma X, Zhao X, Sun Y, Lei H, Xu J, Ma Y, Qi X (2016) Neuroprotective effects of a standardized flavonoid extract from safflower against a rotenone-induced rat model of Parkinson’s disease. Molecules 21(9):1107

    Article  Google Scholar 

  • Akinyemi AJ, Thome GR, Morsch VM, Stefanello N, da Costa P, Cardoso A, Goularte JF, Belló-Klein A, Akindahunsi AA, Oboh G, Schetinger MR (2016) Effect of dietary supplementation of ginger and turmeric rhizomes on ectonucleotidases, adenosine deaminase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of hypertensive rats. J Appl Biomed 14(1):59–70

    Article  Google Scholar 

  • Alia M, Horcajo C, Bravo L, Goya L (2003) Effect of grape antioxidant dietary fiber on the total antioxidant capacity and the activity of liver antioxidant enzymes in rat. Nutr Res 23:1251–1267

    Article  CAS  Google Scholar 

  • Azevedo MI, Pereira AF, Nogueira RB, Rolim FE, Brito GA, Wong DV, LimaJúnior RC, de Albuquerque RR, Vale ML (2013) The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain 9:53

    Article  Google Scholar 

  • Babalola OO, Okonji RE, Atoyebi JO, Sennuga TF, Raimi MM, Ejim-Eze EE, Adeniran OA, Akinsiku OT, Areola JO, John OO, Odebunmi SO (2009) Distribution of lead in selected organs and tissues of albino rats exposed to acute lead toxicity. Sci Res Essay 5:845–848

    Google Scholar 

  • Bagatini MD, dos Santos AA, Cardoso AM, Mânica A, Reschke CR, Carvalho FB (2018) The impact of purinergic system enzymes on noncommunicable, neurological, and degenerative diseases. J Immunol Res 2018:1–21

    Google Scholar 

  • Bandaruk Y, Mukai R, Kawamura T, Nemoto H, Terao J (2012) Evaluation of the inhibitory effects of quercetin-related flavonoids and tea catechins on the monoamine oxidase-a reaction in mouse brain mitochondria. J Agric Food Chem 60(41):10270–10277

    Article  CAS  Google Scholar 

  • Borroni E, Bohrmann B, Grueninger F, Prinssen E, Nave S, Loetscher H, Chinta SJ, Rajagopalan S, Rane A, Siddiqui A, Ellenbroek B (2017) Sembragiline: a novel, selective monoamine oxidase type B inhibitor for the treatment of Alzheimer’s disease. J Pharmacol Exp Ther 362(3):413–423

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Brundege JM, Dunwiddie TV (1997) Role of adenosine as a modulator of synaptic activity in the central nervous system. In Advances in pharmacology, Academic Press, Cambridge 39:353–391

  • Burnstock G (2006) Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 27:166–176

    Article  CAS  Google Scholar 

  • Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797

    Article  CAS  Google Scholar 

  • Burnstock G (2009) Autonomic neurotransmission: 60 years since sir Henry dale. Annu Rev Pharmacol Toxicol 49:1–30

    Article  CAS  Google Scholar 

  • Chan KM, Delfert D, Junger KD (1986) A direct colorimetric assay for Ca2+stimulated ATPase activity. Anal Biochem 157(2):375–380

    Article  CAS  Google Scholar 

  • Chen X, Zhou H, Li X, Wang Z, Zhu G, Jin T (2015) Effects of lead and cadmium co-exposure on hemoglobin in a Chinese population. Environ Toxicol Pharmacol 39(2):758–763

    Article  CAS  Google Scholar 

  • Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 283–284

    Google Scholar 

  • Cunha RA, Ribeiro JA (2000) ATP as presynaptic modulator. Life Sci 68:119–137

    Article  CAS  Google Scholar 

  • da Costa P, Gonçalves JF, Baldissarelli J, Mann TR, Abdalla FH, Fiorenza AM, da Rosa MM, Carvalho FB, Gutierres JM, de Andrade CM, Rubin MA (2017) Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium. Environ Toxicol 32(1):70–83

    Article  Google Scholar 

  • De Mendonca A, Almeida T, Bashir ZI, Ribeiro JA (1997) Endogenous adenosine attenuates long-term depression and depotentiation in the CA1 region of the rat hippocampus. Neuropharmacology 36:161–167

    Article  Google Scholar 

  • Devi WB, Sengottuvelu S, HajaShrief S, Lalitha V, Sivakumar T (2011) Memory enhancing activities of Ficus religiosa leaves in rodents. Int J Res Ayurveda Pharm 2:834–838

    Google Scholar 

  • Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24(1):31–55

    Article  CAS  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  Google Scholar 

  • Flora SJ, Mittal M, Mehta A (2008) Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res 128(4):501–523

    CAS  PubMed  Google Scholar 

  • Foyet HS, Abaïssou HH, Wado E, Acha EA, Alin C (2015) Emilia coccinae (SIMS) G extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in scopolamine-treated rats. BMC Complement Altern Med 15(1):333

    Article  Google Scholar 

  • Green AL, Haughton TM (1961) Colorimetric method for the estimation of monoamine oxidase. Biochem J 78:172–175

    Article  CAS  Google Scholar 

  • Guisti G, Galanti B (1984) Methods of Enzymatic Analyses. VerlagChemie, Weinheim, pp 315–323

    Google Scholar 

  • He ZL, Yang XE, Stoffella PJ (2005) Trace elements in agroecosystems and impacts on the environment. J Trace Elem Med Biol 19(2–3):125–140

    Article  CAS  Google Scholar 

  • Hernández LE, Sobrino-Plata J, Montero-Palmero MB, Carrasco-Gil S, Flores-Cáceres ML, Ortega-Villasante C, Escobar C (2015) Contribution of glutathione to the control of cellular redox homeostasis under toxic metal and metalloid stress. J Exp Bot 66(10):2901–2911

    Article  Google Scholar 

  • Heymann D, Reddington M, Kreutzberg GW (1984) Subcellular localization of 5′- nucleotidase in rat brain. J Neurochem 43(4):971–978

    Article  CAS  Google Scholar 

  • Hou WC, Lin RD, Chen CT, Lee MH (2005) Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla. J Ethnopharmacol 100:216–220

    Article  CAS  Google Scholar 

  • Hu QH, Wang C, Li JM, Zhang DM, Kong LD (2009) Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement. Am J Physiol Ren Physiol 297(4):F1080–F1091

    Article  CAS  Google Scholar 

  • Ignat I, Volf I, Popa VI (2011) A critical review of methods for characterisation of polyphenolic compounds in fruits and vegetables. Food Chem 126(4):1821–1835

    Article  CAS  Google Scholar 

  • Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345:91–104

    Article  CAS  Google Scholar 

  • Kamalakkannan N, Prince PS (2006) Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic Clin Pharmacol Toxicol 98:97–103

    Article  CAS  Google Scholar 

  • Kamel KM, Abd El-Raouf OM, Metwally SA, Abd El-Latif HA, El-sayed ME (2014) Hesperidin and rutin, antioxidant citrus flavonoids, attenuate cisplatin-induced nephrotoxicity in rats. J Biochem Mol Toxicol 28(7):312–319

    Article  CAS  Google Scholar 

  • Karri V, Schuhmacher M, Kumar V (2016) Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: a general review of metal mixture mechanism in brain. Environ Toxicol Pharmacol 48:203–213

    Article  CAS  Google Scholar 

  • Kepp O, Loos F, Liu P, Kroemer G (2017) Extracellular nucleosides and nucleotides as immunomodulators. Immunol Rev 280(1):83–92

    Article  CAS  Google Scholar 

  • Kesavan P, Banerjee A, Banerjee A, Murugesan R, Marotta F, Pathak S (2018) An overview of dietary polyphenols and their therapeutic effects. In: Polyphenols: Mechanisms of Action in Human Health and Disease. Academic Press, Cambridge, pp 221–235

    Chapter  Google Scholar 

  • Khan MH, Parvez S (2015) Hesperidin ameliorates heavy metal induced toxicity mediated by oxidative stress in brain of Wistar rats. J Trace Elem Med Biol 31:53–60

    Article  CAS  Google Scholar 

  • Kumar A, Singh N, Pandey R, Gupta VK, Sharma B (2018) Biochemical and molecular targets of heavy metals and their actions. In: Biomedical Applications of Metals. Springer, Cham, pp 297–319

    Chapter  Google Scholar 

  • Lee MH, Lin RD, Shen LY, Yang LL, Yen KY, Hou WC (2001) Monoamine oxidase B and free radical scavenging activities of natural flavonoids in Melastoma candidum D. Don. J Agric Food Chem 49(11):5551–5555

    Article  CAS  Google Scholar 

  • Limón-Pacheco J, Gonsebatt ME (2009) The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutation Res 674(1–2):137–147

    Article  Google Scholar 

  • Lochhead JJ, McCaffrey G, Quigley CE, Finch J, DeMarco KM, Nametz N, Davis TP (2010) Oxidative stress increases blood–brain barrier permeability and induces alterations in occludin during hypoxia–reoxygenation. J Cereb Blood Flow Metab 30(9):1625–1636

    Article  CAS  Google Scholar 

  • Méndez-Armenta M, Ríos C (2007) Cadmium neurotoxicity. Environ Toxicol Pharmacol 23(3):350–358

    Article  Google Scholar 

  • Nemmiche S, Chabane-Sari D, Guiraud P (2007) Role of α-tocopherol in cadmium-induced oxidative stress in Wistar rat's blood, liver and brain. Chem Biol Interact 170(3):221–230

    Article  CAS  Google Scholar 

  • Nna VU, Ujah GA, Mohamed M, Etim KB, Igba BO, Augustine ER, Osim EE (2017) Cadmium chloride–induced testicular toxicity in male wistar rats; prophylactic effect of quercetin, and assessment of testicular recovery following cadmium chloride withdrawal. Biomed Pharmacother 94:109–23

  • North RA, Verkhratsky A (2006) Purinergic transmission in the central nervous system. Pflugers Arch 452:479–485

    Article  CAS  Google Scholar 

  • Nwanna EE, Adebayo AA, Oboh G, Ogunsuyi OB, Ademosun AO (2019) Modulatory effects of alkaloid extract from Gongronemalatifolium (Utazi) and Lasiantheraafricana (Editan) on activities of enzymes relevant to neurodegeneration. J Diet Suppl 16(1):27–39

    Article  CAS  Google Scholar 

  • Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood-brain barrier. Nat Med 19(12):1584–1596

    Article  CAS  Google Scholar 

  • Ognjanović BI, Marković SD, Pavlović SZ, Žikić RV, Štajn AŠ (2008) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res 57(3)

  • Panchal SK, Poudyal H, Arumugam TV, Brown L (2011) Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats. J Nutr 141(6):1062–1069

    Article  CAS  Google Scholar 

  • Poujois A, Devedjian JC, Moreau C, Devos D, Chaine P, Woimant F, Duce JA (2016) Bioavailable trace metals in neurological diseases. Curr Treat Options Neurol 18(10):46

    Article  Google Scholar 

  • Renugadevi J, Prabu SM (2010) Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 62(2):171–181

    Article  CAS  Google Scholar 

  • Robson S, Sévigny J, Zimmermann H (2006) The E-NTPDase family of ectonucleotidases: structure function relationships and pathophysiological significance. Purinergic Signal 2:409–430

    Article  CAS  Google Scholar 

  • Saaby L, Rasmussen HB, Jager AK (2009) MAO-A inhibitory activity of quercetin from Calluna vulgaris (L.) Hull. J Ethnopharmacol 121:178–181

    Article  CAS  Google Scholar 

  • Safarzadeh E, Jadidi-Niaragh F, Motallebnezhad M, Yousefi M (2016) The role of adenosine and adenosine receptors in the immunopathogenesis of multiple sclerosis. Inflamm Res 65(7):511–520

    Article  CAS  Google Scholar 

  • Schetinger MR, Porto NM, Moretto MB, Morsch VM, da Rocha JB, Vieira V, Moro F, Neis RT, Bittencourt S, Bonacorso HG, Zanatta N (2000) New benzodiazepines alter acetylcholinesterase and ATPDase activities. Neurochem Res 25(7):949–955

    Article  CAS  Google Scholar 

  • Scullin MK, Bliwise DL (2015) Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research. Perspect Psychol Sci 10(1):97–137

    Article  Google Scholar 

  • Shukla A, Shukla GS, Srimal RC (1996) Cadmium-induced alterations in blood-brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat. Hum Exp Toxicol 15:400–405

    Article  CAS  Google Scholar 

  • Sloley BD, Urichuk LJ, Morley P, Durkin J, Shan JJ, Pang PK, Coutts RT (2000) Identification of kaempferol as a monoamine oxidase inhibitor and potential neuroprotectant in extracts of Ginkgo biloba leaves. J Pharm Pharmacol 52(4):451–459

    Article  CAS  Google Scholar 

  • Solanki I, Parihar P, Mansuri ML, Parihar MS (2015) Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 6(1):64–72

    Article  CAS  Google Scholar 

  • Sperlágh B, Vizi E, Wirkner K (2006) P2X7 receptors in the nervous system. Prog Neurobiol 78:327–346

    Article  Google Scholar 

  • Thomas T (2000) Monoamine oxidase-B inhibitors in the treatment of Alzheimers disease. Neurobiol Aging 21(2):343–348

  • Tian R, Yang W, Xue Q, Gao L, Huo J, Ren D, Chen X (2018) Rutin ameliorates diabetic neuropathy by lowering plasma glucose and decreasing oxidative stress via Nrf2 signaling pathway in rats. Eur J Pharmacol 771:84–92

  • Ujah GA, Nna VU, Agah MI, Omue LO, Leku CB, Osim EE (2018) Effect of quercetin on cadmium chloride-induced impairments in sexual behaviour and steroidogenesis in male Wistar rats. Andrologia 50(2):e12866

  • Wieraszko A (1996) Extracellular ATP as a neurotransmitter: its role in synaptic plasticity in the hippocampus. Acta Neurobiol Exp (Wars) 56:637–648

    CAS  Google Scholar 

  • Yegutkin GG (2008) Nucleotide-and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochemica et Biophysica Acta 1783(5):673–694

    Article  CAS  Google Scholar 

  • Yokel RA (2006) Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimers Dis 10(2–3):223–253

    Article  Google Scholar 

  • Youdim MB, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7(4):295–309

    Article  CAS  Google Scholar 

  • Zimmermann H (2006) Nucleotide signaling in nervous system development. Pflugers Arch 452(5):573–588

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Functional Foods and Nutraceutical Research Laboratory, Biochemistry Department, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria

    Ganiyu Oboh, Adeniyi A. Adebayo, Ayokunle O. Ademosun & Olanike G. Olowokere

Authors
  1. Ganiyu Oboh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adeniyi A. Adebayo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayokunle O. Ademosun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olanike G. Olowokere
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ganiyu Oboh or Adeniyi A. Adebayo.

Ethics declarations

Conflict of interest

None to declare.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oboh, G., Adebayo, A.A., Ademosun, A.O. et al. Rutin alleviates cadmium-induced neurotoxicity in Wistar rats: involvement of modulation of nucleotide-degrading enzymes and monoamine oxidase. Metab Brain Dis 34, 1181–1190 (2019). https://doi.org/10.1007/s11011-019-00413-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-019-00413-4

Keywords

Search

Navigation