Main Article Content
Aims: Lead (II) acetate 3-hydrate also known as lead acetate is a neurotoxin that accumulates in soft tissues and bones causing damage to the nervous system of the human body. Hence, this study investigated the effect of short-term administration of Lead (II) Acetate 3-hydrate on serotonin, melatonin, (Na+, K+)-ATPase enzyme activity and neurocognition.
Methodology: Female Wistar rats (150-200 g b.wgt) were divided into groups (n=14). Control group (n=7) received 0.5 ml of normal saline and the treated group (n=7) were administered lead (II) acetate 3-hydrate at 100mg/kg for seven (7) days intraperitoneally (IP). Serotonin (5-HT), Melatonin and Sodium/Potassium-Adenosine Triphosphate [(Na+, K+)-ATPase] enzyme was investigated in the brain tissue and neurobehavior: Tail suspension test (TST), Forced swimming test (FST) and Novel object recognition test (NORT) were investigated. Body weight of the rats was also taken daily.
Results: The result obtained revealed significant (P<0.05) decrease in body weight in the treated group. Neurobehavioral results investigated showed a significant (P<0.05) increase immobility time both in FST and TST and a significant (P<0.05) decrease in retention latency in the NORT. The biochemical analysis reveals a significant (P<0.05) increase level of serotonin (5HT), but melatonin and (Na+, K+)-ATPase enzyme activity decreased significantly (P<0.05) when compared with the control group.
Conclusion: This current study shows that lead (II) acetate 3-hydrate affect neurocognition and can possibly initiate depressive-like behavior via melatonin and serotonin imbalance and also tampering with the (Na+, K+)-ATPase mechanism in the brain mitochondria.
Staudinger KC, Roth VS. Occupational lead poisoning. Am Fam Physician. 1998; 57(4):719 26,731–2.
Menke A, Muntner P, Batuman P, Silbergeld EK, Guallar E. Blood lead below 0.48 micromol/L (10 microgL) and mortality among US adults. Circulation. 2006;114: 1388–1394.
Shukla PK, Khanna VK, Khan MY, Srimal RC. Protective effect of curcumin against lead neurotoxicity in rat. Hum Exp Toxicol. 2003;12:653–658.
Hossain S, Bhowmick S, Jahan S, Rozario L, Sarkar M, Islam S, Basunia MA, Rahman A, Choudhury BK, Shahjalal H. Maternal lead exposure decreases the levels of brain development and cognition-related proteins with concomitant upsurges of oxidative stress, inflammatory response and apoptosis in the offspring rats. Neurotoxicol. 2016;56:150–158.
Grant LD. Lead and compounds. Environmental Toxicant. 2009;27:627-75.
Park SK, O'Neill MS, Vokonas PS, Sparrow D, Wright RO, Coull B, Nie H, Hu H. Air pollution and heart rate variability: effect Modification by Chronic Lead Exposure. Epidemiology (Cambridge, Mass.). 2008;19(1):111–20.
Kosnett MJ, Wedeen RP, Rothenberg SJ, Hipkins KL, Materna BL, Schwartz BS, Hu H, Woolf A. Recommendations for Medical Management of Adult Lead Exposure. Environmental Health Perspectives. 2007; 115(3):463–71.
Cleveland LM, Minter ML, Cobb KA, Scott AA, German VF. Lead hazards for pregnant women and children: part 1: immigrants and the poor shoulder most of the burden of lead exposure in this country. Part 1 of a two-part article details how exposure happens, whom it affects, and the harm it can do. Am J Nurs. 2008; 108:40–49.
Goldstein GW. Evidence that lead acts as a calcium substitute in second messenger metabolism. Neuro Toxicology. 1993;14(2): 3:97–102.
Verity MA, Goyer RA, Klaassen CD, Waalkes MP. Nervous system. Metal Toxicology. 1995;199–226.
Frazer A, Hensler JG. Understanding the neuroanatomical organization of serotonergic cells in the brain provides insight into the functions of this neurotransmitter. Basic Neurochemistry; 1999.
Blier P, Mansari EI. Serotonin and beyond: Therapeutic for major depression. Biological Sciences. 2013;368(1615): 20120536.
Chilmonczyk Z, Bojarski AJ, Pilc A, Sylte I. Functional selectivity and antidepressant activity of serotonin 1A receptor ligands. International Journal of Molecular Sciences. 2015;16(8):18474-506.
Sharafati-Chaleshtori R, Shirzad H, Rafieian-Kopaei M, Soltani A. Melatonin and human mitochondrial diseases. Journal of Research in Medical Sciences. 2017;22:2.
Faraone, Stephen V. ADHD: Non-Pharmacologic Interventions, An Issue of Child and Adolescent Psychiatric Clinics of North America. 2014;888.
Auld F, Maschauer EL, Morrison I, Skene DJ, Riha RL. Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Medicine Reviews. 2017;34:10–22.
Boutin JA, Audinot V, Ferry G, Delagrange P. Molecular tools to study melatonin pathways and actions. Trends in Pharmacological Sciences. 2005;26(8): 412–9.
Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005;27(2):119–30.
Goldstein G. W. Evidence that lead acts asa calcium substitute in second messengermetabolism. NeuroToxicology. 1993;14(2):3,97–102.
Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu SS, Calcium ATP. ROS: A mitochondrial love-hatetriangle. American Journal of Physiology. 2004;287 (4):817-833.
Beltran B, Quintero M, Garcia-Zaragoza E, O’Connor E, Esplugues JV, Moncada S. Inhibition of mitochondrial respiration by endogenous nitric oxide: a critical step in Fas signaling. Proc Natl Acad Sci. 2002; 99:8892– 8897.
Arrell DK, Elliott ST, Kane LA, Guo Y, Ko YH, Pedersen PL, Robinson J, Murata M, Murphy AM, Marban E, Van Eyk JE. Proteomic analysis of pharmacological preconditioning: novel protein targets converge to mitochondrial metabolism pathways. Circ Res. 2006;99:706–714.
Roy M, David N, Cueva M. and Giorgetti M. A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression. Biological Psychiatry. 2007;61:174-180.
Steru L, Chermat R, Thierry B, Simon P. The tail suspension test — A new method for screening antidepressants in mice. Psychopharmacology. 1985;85:367–370.
Guragac Dereli FT, Ilhan M, Kupeli Akkol E. Discovery of new antidepressant agents: In vivo study on Anthemis wiedemanniana Fisch. & Mey. J. Ethnopharmacol. 2018;226:11–16.
Steckler T, Drinkenburg W. H, Sahgal A, Aggleton J. P. Recognition memory in rats - I. Concepts and classification. ProgNeurobiol. 1998;54(3):289-311.
Imam Z, Newport GD, Islam F, Slikker Jr. W, Ali SF. Selenium: An antioxidant protects against methamphetamine induced dopaminergic neurotoxicity. Brain Res. 1999;818:515-578.
Hardeland R, Reiter RJ, Poeggeler B, Tan DX. The significance of the metabolism of the neurohormone melatonin: Antioxidative protection and formation of bioactive substances. Neuroscience and Biobehavioral Review. 1993;17:347-357.
Rais I, Karas M, Schagger H. Two-dimensional electrophoresis for the isolation of integral membrane proteins and mass spectrometric identification. Proteomics. 2004;4:2567–2571.
Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clinics in Geriatric Medicine. 2014;30(3):421–442.
Kandel ER, Schwartz JH, Jessel TM. Overview of synaptic transmission. Principles of Neural Science. 2000;4: 1227-1246.
Ghazanfarpour E, Fatei M, Ghandehari F. Protective effect of Lactobacillus fermentum on Lead-induced hematological and body weight alteration in rats. Iran J Toxicol. 2019;3(3):15-20.
Saritha S, Davuljigari CB, Kumar KP, Reddy GR. Effects of combined arsenic and led exposure on the brain monoaminergic system and neurobehavioral functions in rats: reversal effect of MiADMSA. Toxicology and Industrial health. 2019;35(2):89-108.
Dillion GM, Shelton D, McKinney AP, Caniaga M, Marcus JN, Ferguson MT, Kornecook TJ, Dodart JC. Prefrontal cortex lesions and scopolamine impair attention performance of C57BL/6 mice in novel 2-choice visual discrimination task. Behavioural Brain Research. 2009;204: 67-76.
Chen F, Zhou CC, Yang Y, Liu JW, Yan CH. Gm1 ameliorates lead-induced cognitive deficits and brain damaged through activating the SIRT1/ CREB/ BDNF pathway in the developing male rat hippocampus. Biological Trace Element Research. 2019;190(2):425-436.
Sansar W, Bouyatas M. M, Ahboucha S, Gamrani H. Effect of chronic lead intoxication on rat serotoninergic system and anxiety behavior. Acta Histochemica. 2012;114(1):41-45.
Benammi H, El Hiba O, Romane A, Gamrani H. A blunted anxiolytic like effect of curcumin against acute lead induced anxiety in rat: involvement of serotonin. Acta Histochemica. 2014;116(5):920- 925
Al Omar SY, Fahad AA, Moneim AE, Metwally DM, El-khadragy MF, Kassab R. B. The neuroprotective role of coenzyme Q10 against lead acetate-induced neurotoxity is mediated by antioxidant, anti-inflammatory anti-apoptotic activities. International Journal of Environmental Research and Public Health. 2019;16(16).
Gurer-Orhan H, and Suzen S. Melatonin, its metabolites and its synthetic analogs as multi-faceted compounds: Antioxidant, prooxidant and inhibitor of bioactivation reactions. Current medicinal chemistry. 2015;22(4):490-499.
Reiter RJ, Rosales-Corral S, Tan DX, Jou MJ, Galano A, Xu B. Melatonin as a mitochondria-targeted antioxidant: One of evolution's best ideas. Cellular and Molecular Life Sciences. 2017;74(21): 3863–3881.
Maestroni GJ. The immunotherapeutic potential of melatonin. Expert Opinion on Investigational Drugs. 2001;10(3):467– 76.
Jockers R, Delagrange P, Dubocovich M. L, Markus RP, Renault N, Tosini G. Update on melatonin receptors: IUPHAR Review 20. British Journal of Pharmacology. 2016; 173(18):2702–25.
Jonckheere A. L, Smeitink J. A, Rodenburg R. J. Mitochondrial ATP synthase: architecture, function and pathology. Journal of Inherited Metabolic Disease. 2012;35(2):211-225.
Giorgio V, Von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, Glick G. D, Petronilli V, Zoratti M, Szabo I, Lippe G. Dimmers of mitochondrial ATP synthase fro the permeability transition pore. Proceedings of the National Academy of Sciences. 2013;110(15):5887-5892.