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Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model

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Abstract

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes has been reported to exert cognitive enhancing potential with limited scientific basis. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in cadmium (Cd)-induced memory impairment in rats. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage for 7 days. The results of this study revealed that cerebral cortex AChE and ADA activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed these activities to the control levels. Furthermore, Cd intoxication increased the level of lipid peroxidation in cerebral cortex with a concomitant decreased in functional sulfuhydryl (−SH) group and nitric oxide (NO), a potent neurotransmitter and neuromodulatory agent. However, the co-treatment with curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde (MDA) level. Therefore, inhibition of AChE and ADA activities as well as increased antioxidant status by curcumin in Cd-induced memory dysfunction could suggest some possible mechanism of action for their cognitive enhancing properties.

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References

  • Abdalla FH, Cardoso AC, Pereira LB, Schmatz R, Goncalves JF, Stefanello N, Fiorenza AM, Gutierres JM, Serres JDS, Zanini D, Pimentel VC, Vieira JM, Schetinger MRC, Morsch VM, Mazzanti CM (2013) Neuroprotective effect of quercetin in ectoenzymes and acetylcholinesterase activities in cerebral cortex synaptosomes of cadmium-exposed rats. Mol Cell Biochem 381:1–8

    Article  CAS  PubMed  Google Scholar 

  • Abdalla FH, Schmatz R, Cardoso AC, Carvalho FB, Baldissarelli J, de Oliveira JS, Rosa MM, Goncalves Nunes MA, Rubin MA, da Cruz IB, Barbisan F, Dressler VL, Pereira LB, Schetinger MR, Morsch VM, Goncalves JF, Mazzanti CM (2014) Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: possible involvement of the acetylcholinesterase and Na1, K1- ATPase activities. Physiol Behav 135:152–167

    Article  CAS  PubMed  Google Scholar 

  • Adeniyi PA, Ishola AO, Laoye BJ, Olatunji BP, Bankole OO, Shallie PD, Ogundele OM (2016) Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment. Metab Brain Dis 30:15

    Google Scholar 

  • Akinyemi AJ, Thome GR, Morsch VM, Stefanello N, da Costa P, Cardoso A, Goularte JF, Bello-Klein A, Akindahunsi AA, Oboh G, Schetinger MRC (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 14:59–70

    Article  Google Scholar 

  • Anamika B (2012) Extraction of curcumin. J environ Sci Toxicol. Food Technol 1:1–16

    Google Scholar 

  • Bauerle JD, Grenz A, Kim JH, Lee HT, Eltzschig HK (2011) Adenosine generation and signaling during acute kidney injury. J Am Soc Nephrol 22:14–20

    Article  CAS  PubMed  Google Scholar 

  • Bouayed J, Rammal H, Soulimani R (2009) Oxidative stress and anxiety. Oxidative Med Cell Longev 2:63–67

    Article  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:218–254

    Article  Google Scholar 

  • Burnstock G (2006) Purinergic signalling. Br J Pharmacol 147:172–181

    Article  Google Scholar 

  • Carageorgiou H, Tzotzes V, Sideris A, Zarros A, Tsakiris S (2005) Cadmium effects on brain acetylcholinesterase activity and antioxidant status of adult rats: modulation by zinc, calcium and L-cysteine co-administration. Basic Clin Pharmacol Toxicol 97:320–324

    Article  CAS  PubMed  Google Scholar 

  • Chacon MA, Reyes AE, Inestrosa NC (2003) Acetylcholinesterase induces neuronal cell loss, astrocyte hypertrophy and behavioral deficits in mammalian hippocampus. J Neurochem 87:195–204

    Article  CAS  PubMed  Google Scholar 

  • Costa P, Goncalves JF, Baldissarelli J, Mann TR, Abdalla FH, Fiorenza AM, da Rosa MM, Carvalho FB, Gutierres JM, de Andrade CM, Rubin MA, Schetinger MRC, Morsch VM (2015) Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium. Environ Toxicol doi:10.1002/tox.22213.

  • Deiana S, Platt B, Riedel G (2011) The cholinergic system and spatial learning. Behav Brain Res 221:389–411

    Article  CAS  PubMed  Google Scholar 

  • Desrosiers MD, Cembrola KM, Fakir MJ, Stephens LA, Jama FM, Shameli A, Mehal WZ, Santamaria P, Shi Y (2007) Adenosine deamination sustains dendritic cell activation in inflammation. J Immunol 179:1884–1892

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

  • Fukao M, Hattori Y, Kanno M, Sakuma I, Kitabatake A (1997) Sources of Ca2+ in relation to generation of acetylcholine-induced endothelium-dependent hyperpolarization in rat mesenteric artery. Br J Pharmacol 120:1328–1334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KTS (2015) The role of the nitric oxide pathway in brain injury and its treatment — from bench to bedside. Exp Neurol 263:235–243

    Article  CAS  PubMed  Google Scholar 

  • Garthwaite J, Boulton CL (1995) Nitric oxide signaling in the nervous system. Annu Rev Physiol 57:683–706

    Article  CAS  PubMed  Google Scholar 

  • Goncalves JF, Fiorenza AM, Spanevello RM, Mazzanti CM, Bochi GV, Antes FG, Stefanello N, Rubin MA, Dressler VL, Morsch VM, Schetinger MR (2010) N-acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium. Chem Biol Interact 186:53–60

    Article  CAS  PubMed  Google Scholar 

  • Goncalves JF, Nicoloso FT, da Costa P, Farias JG, Carvalho FB, da Rosa MM, Gutierres JM, Abdalla FH, Pereira JS, Dias GR, Barbosa NB, Dressler VL, Rubin MA, Morsch VM, Schetinger MR (2012) Behavior and brain enzymatic changes after longterm intoxication with cadmium salt or contaminated potatoes. Food Chem Toxicol 50:3709–3718

    Article  CAS  PubMed  Google Scholar 

  • Griffiths S, Scott H, Glover C, Bienenmann A, Ghorbel MT, Uney J (2008) Expression of long term depression underlies visual recognition memory. Neuron 58:186–194

    Article  CAS  PubMed  Google Scholar 

  • Guisti G, Galanti B (1984) Colorimetric method. In: Bergmeyer HU (eds) Methods of Enzymatic Analysis, Verlag Chemie Weinheim, pp 315–323

  • Gutierres JM, Carvalho FB, Schetinger MR, Rodrigues MV, Schmatz R, Pimentel VC, Vieira JM, Rosa MM, Marisco P, Ribeiro DA, Leal C, Rubin MA, Mazzanti CM, Spanevello RM (2012) Protective effects of anthocyanins on the ectonucleotidase activity in the impairment of memory induced by scopolamine in adult rats. Life Sci 91:1221–1228

    Article  CAS  PubMed  Google Scholar 

  • Hashiguchi W, Nagatomo I, Akasaki Y, Uchida M, Tominaga M, Takigawa M (2001) Influences of caffeine to nitric oxide production and zonisamide concentration in the brain of seizuresusceptible EL mice. Psychiat. Clin Neurosci 55:319–324

    Article  CAS  Google Scholar 

  • Jaques JAS, Rezer JFP, Ruchel JB, Becker LV, Rosa CS, Souza VCG, Luz SCA, Gutierres JM, Goncalves JF, Morsch VM, Schetinger MRC, Leal DBR (2011) Lung and blood lymphocytes NTPDase and acetylcholinesterase activity in cigarette smoke-exposed rats treated with curcumin. Biom Prev Nutr 1:109–115

    Article  Google Scholar 

  • Jaques JAS, Rezer JFP, Carvalho FB, Rosa MM, Gutierres JM, Goncalves JF, Schmatz R, Bairros AV, Mazzanti CM, Rubin MA, Schetinger MRC, Leal DBR (2012) Curcumin protects against cigarette smoke-induced cognitive impairment and increased acetylcholinesterase activity in rats. Physiol Behav 106:664–669

    Article  CAS  PubMed  Google Scholar 

  • Johri N, Jacquillet G, Unwin R (2010) Heavy metal poisoning: the effects of cadmium on the kidney. BioMetals 23:783–792

    Article  CAS  PubMed  Google Scholar 

  • Klinkenberg I, Sambeth A, Blokland A (2011) Acetylcholine and attention. Behav Brain Res 221:430–442

    Article  CAS  PubMed  Google Scholar 

  • Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K (2007) Effect of curcumin on inflammation and oxidative stress in cisplatin induced experimental nephrotoxicity. J Agric Food Chem 55:10150–10155

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Dogra S, Prakash A (2009) Protective effect of curcumin (Curcuma longa), against aluminium toxicity: possible behavioral and biochemical alterations in rats. Behav Brain Res 205:384–390

    Article  CAS  PubMed  Google Scholar 

  • Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830:3143–3153

    Article  CAS  PubMed  Google Scholar 

  • Mendez-Armenta M, Barroso-Moguel R, Villeda-Hernandez J, Nava-Ruiz C, Rios C (2001) Histopathological alterations in the brain regions of rats after perinatal combined treatment with cadmium and dexamethasone. Toxicol 161:189–199

    Article  CAS  Google Scholar 

  • Mendez-Armenta M, Villeda-Hernandez J, Barroso-Moguel R, Nava-Ruiz C, Jimenez-Capdeville ME, Rios C (2003) Brain regional lipid peroxidation and metallothionein levels of developing rats exposed to cadmium and dexamethasone. Toxicol Lett 144:151–157

    Article  CAS  PubMed  Google Scholar 

  • Miranda KM, Espay MG,Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite.Nitric Oxide 5:62–71

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S, Oskarsson A (2002) Cadmium in blood and urine—impact of sex, age, dietary intake, iron status, and former smoking—association of renal effects. Environ Health Perspect 110:1185–1190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan R, Qiu S, DX L, Dong J (2008) Curcumin improves learning and memory ability and its neuroprotective mechanism in mice. Chinese. Med J 121:832–839

    CAS  Google Scholar 

  • Pari L, Murugavel P (2007) Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicol 234:44–50

    Article  CAS  Google Scholar 

  • Paul V, Ekambaram P (2011) Involvement of nitric oxide in learning & memory processes. Indian J Med Res 133:471–478

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paul V, Subramanian EH (2002) Evidence for an involvement of nitric oxide and raminibutyric acid in the anticonvulsant action of L-arginine on picrotoxin induced convulsions in rats. Pharmacol Biochem Behav 72:515–519

    Article  CAS  PubMed  Google Scholar 

  • Ramani K, Tomasi ML, Yang H, Ko K, SC L (2012) Mechanism and significance of changes in glutamate-cysteine ligase expression during hepatic fibrogenesis. J Biol Chem 287:36341–36355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reeta KH, Mehla J, Gupta YK (2009) Curcumin is protective against phenytoin-induced cognitive impairment and oxidative stress in rats. Brain Res 1301:52–60

    Article  CAS  PubMed  Google Scholar 

  • Schmatz R, Schetinger MRC, Spanevello RM, Mazzanti CM, Stefanello N, Maldonado PA, Gutierres J, Corrêa MC, Girotto E, Moretto MB, Morsch VM (2009) Effects of resveratrol on nucleotide degrading enzymes in streptozotocin induced diabetic rats. Life Sci 84:345–350

    Article  CAS  PubMed  Google Scholar 

  • Shen C, Yang B, Zhou T, Duan G, Yu Y (2011) Bioequivalence evaluation of two brands of rivastigmine of different salt forms, an acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, in healthy Beagle dogs. Pharm 66:590–593

    CAS  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  PubMed  Google Scholar 

  • Sinha M, Manna P, Sil PC (2009) Induction of necrosis in cadmium-induced hepatic oxidative stress and its prevention by the prophylactic properties of taurine. J Trace Elem Med Biol 23:300–313

    Article  CAS  PubMed  Google Scholar 

  • Soreq H, Seidman S (2001) Acetylcholinesterase—new roles for an old actor. Nat Rev Neurosci 2:294–302

    Article  CAS  PubMed  Google Scholar 

  • Strimpakos AS, Sharma RA (2008) Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal 10:511–545

    Article  CAS  PubMed  Google Scholar 

  • Takeda A, Takefuta S, Ijiro H, Okada S, Oku N (1999) Cd transport in rat brain. Brain Res Bull 49:453–459

    Article  CAS  PubMed  Google Scholar 

  • Tang H, Lu D, Pan R, Qin R, Xiong H, Dong J (2009) Curcumin improves spatial memory impairment induced by human immunodeficiency virus type 1 glycoprotein 120 V3 loop peptide in rats. Life Sci 85:1–10

    Article  CAS  PubMed  Google Scholar 

  • Yadav RS, Chandravanshi LP, Shukla RK, Sankhwar ML, Ansari RW, Shukla PK, Pant AB, Khanna VK (2011) Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats. Neurotoxicol 32:760–768

    Article  CAS  Google Scholar 

  • Zalups RK, Ahmad S (2003) Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharmacol 186:163–188

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

One of the authors (Ayodele Jacob Akinyemi) is a beneficiary of 2015 IBRO/ARC bursary award and wish to thank the organization for their support towards this study.

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Authors and Affiliations

  1. Department of Chemical Science, Biochemistry Unit, Afe Babalola University Ado-Ekiti, Private Mail Bag, 5454, Nigeria

    Ayodele Jacob Akinyemi, Princess Kamsy Okonkwo, Sunday Amos Onikanni, Adewale Fadaka & Israel Olayide

  2. Department of Medicine, Ekiti State University Ado-Ekiti, Private Mail Bag, 5363, Nigeria

    Opeyemi Ayodeji Faboya

  3. Department of Clinical Science, Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria

    Opeyemi Ayodeji Faboya

  4. Center for Child and Adolescence Mental Health (CCAMH), College of Medicine, University of Ibadan, Ibadan, Nigeria

    Elizabeth Olufisayo Akinyemi

  5. Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria

    Ganiyu Oboh

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  1. Ayodele Jacob Akinyemi
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  2. Princess Kamsy Okonkwo
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Correspondence to Ayodele Jacob Akinyemi.

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Akinyemi, A.J., Okonkwo, P.K., Faboya, O.A. et al. Curcumin improves episodic memory in cadmium induced memory impairment through inhibition of acetylcholinesterase and adenosine deaminase activities in a rat model. Metab Brain Dis 32, 87–95 (2017). https://doi.org/10.1007/s11011-016-9887-x

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