Document Type : Research Paper


1 PhD student in motor behavior, Faculty of Sports Sciences, Islamic Azad University, Isfahan Branch (Khorasgan), Isfahan, Iran.

2 Qutb Transgenesis Center, Islamic Azad University, Isfahan Branch (Khorasgan), Isfahan, Iran.

3 Faculty member, Faculty of Sports Sciences, Islamic Azad University, Isfahan Branch (Khorasgan), Isfahan, Iran.

4 Faculty of Sports Sciences, Isfahan (Khorasgan)Branch, Islamic Azad University, Isfahan, Iran.

5 Iran National Elite Foundation, Tehran 93111-14578, Iran. - Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.


Lead (Pb) is a toxic metal that causes clinical disorders in the nervous system. This study was conducted with the aim of evaluating the effect of intermittent exercise and curcumin dietary supplement on cognitive, motor and oxidation indices caused by lead nitrate. In this way, 30 male mice of the Balb C breed (25 ± 5 g) were randomly divided into five groups: negative control (healthy), positive control (lead nitrate), curcumin supplement, High intensity interval training (HIIT) and group High intensity interval training (HIIT) with curcumin. were; High intensity interval training protocol (five sessions per week) was performed for six weeks. After the last training session, the cognitive and motor performance of the animals was evaluated with the Y-maze behavioral test, and 24 hours later, the oxidation indices (SOD, CAT, MDA) and the level of lead in the brain tissue were evaluated. Statistical analysis was done by GraphPad Prism software. The findings showed that after exposure to lead, the motor activity in the positive control group (lead nitrate) decreased compared to the negative control group (healthy) (P=0.01) and the curcumin group (0.01), cognitive performance in All the experimental groups had an increase compared to the lead nitrate group. Taking curcumin along with HIIT decreased the lead level compared to the positive control group (P=0.03). Taking curcumin along with HIIT increased the amount of CAT and SOD in the brain. It was found that the combination of curcumin and HIIT reduce the neurotoxicity caused by lead the inhibition of oxidative stress.


Main Subjects

  1. Singh N, Kumar A, Gupta VK, Sharma B. Biochemical and molecular bases of lead-induced toxicity in mammalian systems and possible mitigations. Chem. Res. Toxicol.. 2018 Sep 4;31(10):1009-21.
  2. Sansar W, Gamrani H. The pharmacological effect of Artemisia absinthium extract in protecting adult rats against lead neurotoxicity. J. Neurol. Sci.. 2013 Oct 15;333:e598..
  3. Chintapanti S, Pratap Reddy K, Sreenivasula Reddy P. Behavioral and neurochemical consequences of perinatal exposure to lead in adult male Wistar rats: protective effect by Centella asiatica. Environ. Sci. Pollut. Res. 2018 May;25:13173-85.
  4. Daniel S, Limson JL, Dairam A, Watkins GM, Daya S. Through metal binding, curcumin protects against lead-and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J. Inorg. Biochem. 2004 Feb 1;98(2):266-75.
  5. Candan N, Tuzmen N. Very rapid quantification of malondialdehyde (MDA) in rat brain exposed to lead, aluminium and phenolic antioxidants by high-performance liquid chromatography-fluorescence detection. Neurotoxicology. 2008 Jul 1;29(4):708-13.
  6. Villeda-Hernandez J, Barroso-Moguel R, Mendez-Armenta M, Nava-Ruız C, Huerta-Romero R, Rıos C. Enhanced brain regional lipid peroxidation in developing rats exposed to low level lead acetate. Brain Res. Bull.2001 May 15;55(2):247-51.
  7. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, Haghighi S, Sameni HR, Pahlvan S. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur. J. Pharmacol.. 2011 Sep 30;667(1-3):222-9.
  8. Behnam Rassouli M, Ghayour N, Afsharian M, Tehranipour M, Ghayour MB. The protective effects of Melissa officinalis leaves usage on learning disorder induced by lead acetate administration during pre and postnatal periods in rats. J. Arak Univ. Med. Sci. 2010 Apr 10;13(1):97-104.
  9. Flora SJ, Pachauri V. Chelation in metal intoxication. Int. J. Environ. Res. Public Health. 2010 Jul;7(7):2745-88.
  10. Mohammed Raouf GA, Vaibhav K, Khan A, Tabassum R, Ahmed ME, Javed H, Chander K, Islam F, Siddiqui MS. Terminalia arjuna bark extract inhibits histological alterations by mitigating oxidative stress in lead intoxicated mice. Orient. Pharm. Exp. Med. 2013 Dec;13:253-65.
  11. Aldahmash BA, El-Nagar DM. Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice. Saudi J. Biol. Sci. 2016 Nov 1;23(6):667-73.
  12. Radad K, Hassanein K, Al-Shraim M, Moldzio R, Rausch WD. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats. Exp. Toxicol. Pathol. 2014 Jan 1;66(1):13-7.
  13. Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers of lead exposure: a review. Rev. Environ. Health. 2009 Mar 1;24(1):15-46.
  14. Mansouri MT, Cauli O. Motor alterations induced by chronic lead exposure. Environ. Toxicol. Pharmacol. 2009 May 1;27(3):307-13.
  15. Garza A, Vega R, Soto E. Cellular mechanisms of lead neurotoxicity. Med. Sci. Monit.. 2006 Mar 1;12(3):RA57.
  16. Chen HH, Ma T, Hume AS, Ho IK. Developmental lead exposure alters the distribution of protein kinase C activity in the rat hippocampus. Biomed. Environ. Sci. 1998 Mar 1;11(1):61-9.
  17. Nehru B, Sidhu P. Neurotoxic effects of differential doses of lead on rat brain followed by recovery. J. Trace Elem. Exp. Med. 2002;15(3):131-40.
  18. Sabbar M, Delaville C, De Deurwaerdère P, Lakhdar-Ghazal N, Benazzouz A. Lead-induced atypical Parkinsonism in rats: Behavioral, electrophysiological, and neurochemical evidence for a role of noradrenaline depletion. Front. Neurosci. 2018 Mar 19;12:173.
  19. Barkur RR, Bairy LK. Histological study on hippocampus, amygdala and cerebellum following low lead exposure during prenatal and postnatal brain development in rats. Toxicol. Ind. Health. 2016 Jun;32(6):1052-63.
  20. Davis JM, Svendsgaard DJ. Lead and child development. Nature. 1987 Sep 24;329:297-300.
  21. Cory-Slechta DA, Pokora MJ, Widzowski DV. Postnatal lead exposure induces supersensitivity to the stimulus properties of a D2-D3 agonist. Brain Res. 1992 Dec 11;598(1-2):162-72.
  22. Bourjeily N, Suszkiw JB. Developmental cholinotoxicity of lead: loss of septal cholinergic neurons and long-term changes in cholinergic innervation of the hippocampus in perinatally lead-exposed rats. Brain Res. 1997 Oct 17;771(2):319-28.
  23. Kuhlmann AC, McGlothan JL, Guilarte TR. Developmental lead exposure causes spatial learning deficits in adult rats. Neurosci. Lett. 1997 Sep 19;233(2-3):101-4.
  24. Guilarte TR, Toscano CD, McGlothan JL, Weaver SA. Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Neurol. 2003 Jan;53(1):50-6.
  25. Zhou M, Suszkiw JB. Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure. Brain Res. 2004 Feb 27;999(1):142-7.
  26. Flora G, Gupta D, Tiwari A. Preventive efficacy of bulk and nanocurcumin against lead-induced oxidative stress in mice. Biol. Trace Elem. Res. 2013 Apr;152:31-40.
  27. Abubakar K, Muhammad Mailafiya M, Danmaigoro A, Musa Chiroma S, Abdul Rahim EB, Abu Bakar@ Zakaria MZ. Curcumin attenuates lead-induced cerebellar toxicity in rats via chelating activity and inhibition of oxidative stress. Biomolecules. 2019 Sep 6;9(9):453.
  28. Flora SJ, Pachauri V. Chelation in metal intoxication. Int. J. Environ. Res. Public Health. 2010 Jul;7(7):2745-88.
  29. Gomez-Pinilla F. The influences of diet and exercise on mental health through hormesis. Ageing Res. Rev. 2008 Jan 1;7(1):49-62.
  30. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci.2007 Sep 1;30(9):464-72.
  31. Alivand F, Karimzadeh F. The effect of exercise on the memory improvement: a review of cellular and molecular mechanisms. Shefaye Khatam. 2015 Dec 10;3(4):123-30.
  32. Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW. Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neurosci. J. 2005 Jan 1;133(3):853-61.
  33. Johnson RA, Rhodes JS, Jeffrey SL, Garland Jr T, Mitchell GS. Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neurosci. J. 2003 Sep 26;121(1):1-7.


  1. Babri S, Reisi P, Alaei H, Sharifi MR, Mohades G. Effect of forced treadmill exercise on long-term potentiation (LTP) in the dentate gyrus of hippocampus in male rats. Physiology and pharmacology. 2008 May 10;12(1):39-45.
  2. Sinaei M, Nazem F, Alaei H, Talebi A. The role of aerobic exercise training patterns on learning function and memory performance: A review article. FEYZ. 2019 Oct 10;23(5):563-77.‌
  3. Taylor RP, Olsen ME, Starnes JW. Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart. Am.J.Physiol .Physiology.2007 Jan;292(1):H601-7.
  4. Rooks CR, Thom NJ, McCully KK, Dishman RK. Effects of incremental exercise on cerebral oxygenation measured by near-infrared spectroscopy: a systematic review. Prog. Neurobiol.. 2010 Oct 1;92(2):134-50.
  5. Scheede-Bergdahl C, Penkowa M, Hidalgo J, Olsen DB. Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes. Diabetes. 2005 Nov 1;54(11):3089.
  6. Devi SA, Kiran TR. Regional responses in antioxidant system to exercise training and dietary vitamin E in aging rat brain. Neurobiol. Aging. 2004 Apr 1;25(4):501-8.‌
  7. Ferreira TS, Moreira CZ, Cária NZ, Victoriano G, Silva Jr WF, Magalhães JC. Phytotherapy: an introduction to its history, use and application. Rev. Bras. Plant. Med. 2014;16:290-8.
  8. Farid, R.M. A focus on curcumin local application in oral diseases management: Mini review. IOSR J. Pharm. 2016, 6, 30–40.
  9. Mahmoudian-Sani MR, Asadi-Samani M, Luther T, Saeedi-Boroujeni A, Gholamian N. A new approach for treatment of type 1 diabetes: Phytotherapy and phytopharmacology of regulatory T cells. J. Renal Inj. Prev. 2017 Jan 30;6(3):158-63.
  10. García-Niño WR, Pedraza-Chaverrí J. Protective effect of curcumin against heavy metals-induced liver damage. Food Chem. Toxicol. 2014 Jul 1;69:182-201.
  11. Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. J. Agric. Food Chem. 2002 Jun 19;50(13):3668-72.
  12. Hosseinzadeh S, Roshan VD, Mahjoub S. Continuous exercise training and curcumin attenuate changes in brain-derived neurotrophic factor and oxidative stress induced by lead acetate in the hippocampus of male rats. Biol. 2013 Feb 1;51(2):240-5.‌
  13. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. JBC. 2005 Feb 18;280(7):5892-901.‌
  14. Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology. Neurobiol. Aging. 2001 Nov 1;22(6):993-1005.
  15. Sabetkasaei M, Haghparast A, Hajizadeh Moghaddam A, Ataie R, Nasiraei S. The study of the neuroprotective effects of curcumin, against homocysteine intracerebroventricular injection–induced cognition impairment and oxidative stress in the rat. Physiology and Pharmacology. 2009 Nov 10;13(3):328-39.
  16. Hewlings SJ, Kalman DS. Curcumin: A review of its effects on human health. Foods. 2017 Oct 22;6(10):92.
  17. Shi LY, Zhang L, Li H, Liu TL, Lai JC, Wu ZB, Qin J. Protective effects of curcumin on acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. Pharmacol. Rep. 2018 Sep;70:1040-6.
  18. Mary CP, Vijayakumar S, Shankar R. Metal chelating ability and antioxidant properties of Curcumin-metal complexes–A DFT approach. J. Mol. Graphics Modell. 2018 Jan 1;79:1-4.‌
  19. Ebrahimi S, Rashidy-Pour A, Vafaei AA, Mohammad Akhavan M, Haghighi S. Influence of basolateral amygdala lesion on the inhibitory effects of propranolol on voluntary exercise-induced enhancement of learning and memory. Koomesh. 2010 Jan 10;11(2):133-40.
  20. Shukla PK, Khanna VK, Khan MY, Srimal RC. Protective effect of curcumin against lead neurotoxicity in rat. HET. 2003 Dec;22(12):653-8.‌
  21. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M. Chemopreventive and therapeutic effects of curcumin. Cancer Lett. 2005 Jun 8;223(2):181-90.‌


  1. Mohammed Raouf GA, Vaibhav K, Khan A, Tabassum R, Ahmed ME, Javed H, Chander K, Islam F, Siddiqui MS. Terminalia arjuna bark extract inhibits histological alterations by mitigating oxidative stress in lead intoxicated mice.Orient Pharm. Exp. Med.2013 Dec;13:253-65.56.
  2. García-Niño WR, Pedraza-Chaverrí J. Protective effect of curcumin against heavy metals-induced liver damage. FCT. 2014 Jul 1;69:
  3. Amooei M, Meshkati Z, Nasiri R, Dakhili AB. Cognitive decline prevention in offspring of Pb+ 2 exposed mice by maternal aerobic training and Cur/CaCO3@ Cur supplementations: In vitro and in vivo studies. Ecotoxicol. Environ. Saf. 2021 Feb 1;209:111785.
  4. Amoei M, Meshkati Z, Nasiri R, Dakhili AB. The Effect of Aerobic Exercise and Curcumin Diet Supplement on Anxiety Behavior and Locomotor Activity of Female Balb/C Mice Exposed to Lead Nitrate Using the Hole-Board Test. Armaghane Danesh. 2021 Sep 10;26(4):596-610.
  5. Amirkhani Z, Azarbayjani MA, Homaei HM, Peeri M. Effect of combining resistance training and curcumin supplementation on liver enzyme in inactive obese and overweight females. IJDO. 2016 Sep 10;8(3):107-14.
  6. Rezaei S, Matinhomaee H, Azarbayjani MA, Farzanegi P. The effect of intense and moderate interval aerobic exercise and curcumin consumption on the gene expression of c-kit in stem cells of old rats heart. J. Fasa Univ. Med. Sci. 2017;7(1):68-76.
  7. Fu J, Huang Y, Chen H, Wang Y, Yu L, Chu W, Ou X. Beneficial effect of curcumin isolated from Curcuma longa on exercise-induced hepatocyte apoptosis of rat. Int. J. Phys. Sci. 2010;5(7):1081-5.
  8. Elhampour L, Azarbayjani MA, Nasehi M, Piri M, Zarindast MR. Synchronic Effect of Curcumin and swimming training on depression in morphine addicted male mice. J. Med. Plants. 2017 Nov 10;16(64):
  9. Davidson SR, Burnett MA, Hoffman-Goetz L. Training effects in mice after long-term voluntary exercise. Med. Sci. Sports Exercise. 2006 Feb 1;38(2):250-5.
  10. Kraemer WJ, Fleck SJ, Deschenes MR. Exercise physiology: integrating theory and application. Lippincott Williams & Wilkins; 2011 Mar 1.
  11. Dinel AL, Lucas C, Guillemet D, Layé S, Pallet V, Joffre C. Chronic supplementation with a mix of salvia officinalis and salvia lavandulaefolia improves morris water maze learning in normal adult C57Bl/6J mice. Nutrients. 2020 Jun 15;12(6):1777.
  12. Yaghoubi A, Saghebjoo M, Fallah Mohammadi Z, Hedayati M, Hajizadeh Moghaddam A. Effects of continuous training intensity on amyloid beta1-42 (Aβ1-42) levels in hippocampus of homocysteine-induced Alzheimer's Model rats. Arak Med. Univ. J. 2016 Feb 10;18(11):83-93.
  13. Moore TL, Bowley BG, Shultz PL, Calderazzo SM, Shobin EJ, Uprety AR, Rosene DL, Moss MB. Oral curcumin supplementation improves fine motor function in the middle-aged rhesus monkey. Somatosens. Res. 2018 Jan 2;35(1):1-0.
  14. Hosseinzadeh S. Effects of Curcumin supplementation on BDNF and Oxidative/antioxidative process in rat’s hippocampus which exposed to lead. J. Gorgan Univ. Med. Sci. 2011 Jun 10;13(2):1-8.
  15. Khalil SR, Khalifa HA, Abdel-Motal SM, Mohammed HH, Elewa YH, Mahmoud HA. Spirulina platensis attenuates the associated neurobehavioral and inflammatory response impairments in rats exposed to lead acetate. Ecotoxicol. Environ. Saf.. 2018 Aug 15;157:255-65.
  16. Xu Y, Li G, Han C, Sun L, Zhao R, Cui S. Protective effects of Hippophae rhamnoides L. juice on lead-induced neurotoxicity in mice. Biol. Pharm. Bull.. 2005;28(3):490-4.
  17. Altinoz EY, Ozmen T, Oner ZÜ, Elbe H, Erdemli ME, Bag HG. Saffron (its active constituent, crocin) supplementation attenuates lipid peroxidation and protects against tissue injury. Bratisl. Lek. Listy. 2016 Jan 1;117(7):381-7.
  18. Salehi M. Response of brain antioxidant defense system to acute doses of paraxaon in male rats. JAUMS. 2009;7(3):156-62.
  19. Ranjbar AK, Pasalar P, Abdollahi M. Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers. HET. 2002 Apr;21(4):179-82.
  20. Oruç EÖ, Usta D. Evaluation of oxidative stress responses and neurotoxicity potential of diazinon in different tissues of Cyprinus carpio. Environ. Toxicol. Pharmacol.. 2007 Jan 1;23(1):48-55.
  21. Ahmed R, Seth V, Pasha ST, Banerjee BD. Influence of dietary ginger (Zingiber officinales Rosc) on oxidative stress induced by malathion in rats. FCT. 2000 May 1;38(5):443-50.
  22. de Sousa RA, Sabarense CM, Prado GL, Metze K, Cadore S. Lead biomonitoring in different organs of lead intoxicated rats employing GF AAS and different sample preparations. Talanta. 2013 Jan 30;104:90-6.
  23. Simsek N, Akinci L, Alan H, Gecör O, Özan Ü. Determination of trace elements in kidneys, livers and brains of rats with sealer implants by ICP-MS. Biotechnol. Biotechnol. Equip. 2017 Mar 4;31(2):397-402.
  24. Ge Y, Chen L, Sun X, Yin Z, Song X, Li C, Liu J, An Z, Yang X, Ning H. Lead-induced changes of cytoskeletal protein is involved in the pathological basis in mice brain. Environ. Sci. Pollut. Res. 2018 Apr;25:11746-53.
  25. Yu H, Li T, Cui Y, Liao Y, Wang G, Gao L, Zhao F, Jin Y. Effects of lead exposure on D-serine metabolism in the hippocampus of mice at the early developmental stages. Toxicology. 2014 Nov 5;325:189-99.

80. Akbari F, Moghadasi M, Farsi S, Edalatmanesh MA. The Effect of Eight Weeks Moderate-Intensity Endurance Training with Saffron Intake on Memory and Learning in Rats with Trimethytin Model of Alzheimer’s Disease. J. Appl. Physiol. 2019 Dec 22;15(30):115-28.