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Behavioral and neurochemical consequences of perinatal exposure to lead in adult male Wistar rats: protective effect by Centella asiatica

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Abstract

The present study evaluated the protective effects of Centella asiatica (CA) leaf extract on behavioral deficits and neurotoxicity in adult rat exposed to lead during perinatal period. Adult Wistar rats were exposed to 0.15% lead acetate (Pb) from gestation day 6 through drinking water and the pups were exposed lactationally to Pb till weaning. Significant perturbations in locomotor activity and exploratory behavior were observed in rats exposed to Pb during perinatal period. The levels of lipid peroxidation increased significantly with a reduction in levels of glutathione and activity levels of acetylcholinesterase and antioxidant enzymes in hippocampus, cerebrum, cerebellum, and medulla of brains excised from Pb-exposed rats. Oral supplementation of CA during postweaning period provided significant protection against Pb-induced behavioral impairments and neurotoxicity, without chelating tissue Pb levels. The possible neuroprotective efficacy of CA may be due to its antioxidant potential but not by lowering effects of brain Pb content.

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References

  • Aebi H (1984) Catalase in vitro. Meth Enzymol 105:125–126

    Google Scholar 

  • Akerboom TP, Sies H (1981) Assay of glutathione, glutathione disulfide and glutathione mixed disulfides in biological samples. Meth Enzymol 77:373–382

    Article  CAS  Google Scholar 

  • Altmann L, Weinsberg F, Sveinsson K, Lilienthal H, Wiegand H, Winneke G (1993) Impairment of long-term potentiation and learning following chronic lead exposure. Toxicol Lett 66:105–112

    Article  CAS  Google Scholar 

  • Antonio MT, Corpas I, Leret ML (1999) Neurochemical changes in new born rat’s brain after gestational cadmium and lead exposure. Toxicol Lett 104:1–9

    Article  CAS  Google Scholar 

  • Basha DC, Usha Rani M, Devi CB, Ram Kumar M, Reddy GR (2012) Perinatal lead exposure alters postnatal cholinergic and aminergic system in rat brain: reversal effect of calcium co-administration. Int J Dev Neurosci 30:343–350

    Article  CAS  Google Scholar 

  • Bradbury MW, Deane R (1993) Permeability of the blood-brain barrier to lead. Neurotoxicology 14:131–136

    CAS  Google Scholar 

  • Bull RJ, McCauley PT, Taylor DH, Croten KM (1983) The effects of lead on the developing central nervous system of the rat. Neurotoxicology 4:1–17

    CAS  Google Scholar 

  • Burdette LJ, Goldstein R (1986) Long-term behavioral and electrophysiological changes associated with lead exposure at different stages of brain development in the rat. Brain Res 394:101–110

    Article  CAS  Google Scholar 

  • Carlberg I, Mannervik B (1985) Glutathione reductase. Meth Enzymol 113:484–490

    Article  CAS  Google Scholar 

  • Chikezie PC, Chiedozie P, Ibegbulem O, Mbagwu FN (2015) Bioactive principles from medicinal plants. Res J Phytochem 9:88–115

    Article  CAS  Google Scholar 

  • Chopra RN, Nayer SL, Chopra IC, Asolkar LV, Kakkar KK (1994) Glossary of Indian medicinal plants. CSIR Publications, New Delhi

    Google Scholar 

  • CPCSEA (2003) Committee for the Purpose of Control And Supervision of Experiments on Animals: guidelines for laboratory animal facility. Indian J Pharm 35:257–274

    Google Scholar 

  • Crumpton T, Atkin DS, Zawia NH, Barone JRS (2001) Lead exposure to pheochromocytoma (PC12) cells alters neural differentiation and Sp1 DNA-binding. Neurotoxicology 22:49–62

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Duggina P, Kalla CM, Varikasavu SR, Bukke S, Tartte V (2015) Protective effect of Centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action. J Physiol Biochem 71:435–454

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Espejo EF, Mir D (1993) Structure of rat’s behavior in the hot plate test. Behav Brain Res 56:171–176

    Article  CAS  Google Scholar 

  • File SE, Kenny PJ, Cheeta S (2000) The role of the dorsal hippocampal serotonergic and cholinergic systems in the modulation of anxiety. Pharmacol Biochem Behav 66:65–72

    Article  CAS  Google Scholar 

  • Fjerdingstad EJ, Danscher G, Fjerdingstad E (1974) Hippocampus: selective concentration of lead in the normal rat brain. Brain Research 80(2):350–354

    Article  CAS  Google Scholar 

  • Flohe L, Gulzer WA (1984) Glutathione peroxidase. Methods Enzymol 105:114–121

  • Flora SJS, Gupta R (2007) Beneficial effects of Centella asiatica aqueous extract against arsenic-induced oxidative stress and essential metal status in rats. Phytother Res 21:980–988

    Article  CAS  Google Scholar 

  • Hermes-Lima M, Pereira B, Bechara EJH (1991) Are free radicals involved in lead poisoning? Xenobiotica 21:1085–1090

    Article  CAS  Google Scholar 

  • Hussin M, Abdul-Hamid A, Mohamad S, Saari N, Ismail M, Bejo MH (2007) Protective effect of Centella asiatica extract and powder on oxidative stress in rats. Food Chem 100:535–541

    Article  CAS  Google Scholar 

  • Inamdar PK, Yeole RD, Ghogare AB, De Souza NJ (1996) Determination of biologically active constituents in Centella asiatica. J Chromatogr 742:127–130

    Article  CAS  Google Scholar 

  • James JT, Dubery IA (2009) Pentacyclictriterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules 14:3922–3941

    Article  CAS  Google Scholar 

  • Jin Y, Yu F, Liao Y, Liu S, Liu M, Xu J, Yang J (2011) Therapeutic efficiency of succimer used with calcium and ascorbic acid in the treatment of mild lead poisoning. Environ Toxicol Pharmacol 31:137–142

    Article  Google Scholar 

  • Krigman M, Bouldin TW, Mushak P (1980) Lead. In: Spencer P, Schaumburg H (eds) Experimental and clinical neurotoxicology. Williams & Wilkins, Baltimore, pp 490–507

    Google Scholar 

  • Krishnamurthy RG, Senut MC, Zemke D, Min J, Frenkel MB, Greenberg EJ, Yu SW, Ahn N, Goudreau J, Kassab M, Panickar KS, Majid A (2009) Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia. J Neurosci Res 87:2541–2550

    Article  CAS  Google Scholar 

  • Kumar MH, Gupta YK (2003) Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats. J Ethanopharmacol 79:253–260

    Article  Google Scholar 

  • Kumar A, Dogra S, Prakash A (2009) Neuro protective effects of Centella asiatica against intra cerebro-ventricular colchicine induced cognitive impairment and oxidative stress. Int J Alzheimers Dis 2009:1–8

    Article  Google Scholar 

  • Kuroda M, Mimaki Y, Harada H, Sakagami H, Sashida Y (2001) Five new triterpene glycosides from Centella asiatica. Nat Med 55:134–138

    CAS  Google Scholar 

  • Leret ML, Antonia JSM, Antonia MT (2003) Perinatal exposure to lead and cadmium affects anxiety-like behavior. Behav Toxicol 186:125–130

    Article  CAS  Google Scholar 

  • Lidsky TI, Schineder JS (2003) Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5–19

    Article  Google Scholar 

  • Lowry LH, Rosebrough NI, Farr AL, Randall RJ (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  • Ma T, Chen HH, Ho IK (1999) Effects of chronic lead (Pb) exposure on neurobehavioral function and dopaminergic neurotransmitter receptors in rats. Toxicol Lett 105:111–121

    Article  CAS  Google Scholar 

  • Marques NF, Stefanello ST, Froeder AL, Busanello A, Boligon AA, Athayde ML, Soares PA, Fachinetto R (2015) Centella asiatica and its fractions reduces lipid peroxidation induced by quinolinic acid and sodium nitroprusside in rat brain regions. Neurochem Res 40:1197–1210

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Moreira EG, Vassilieff I, Vassilieff VS (2001) Developmental lead exposure: behavioral alterations in the short and long term. Neurotoxicol Teratol 23:489–495

    Article  CAS  Google Scholar 

  • Morris RGM (1984) Developments of water maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60

    Article  CAS  Google Scholar 

  • Mylroie AA, Umbles C, Kyle J (1984) Effects of dietary copper supplementation on erythrocyte superoxide dismutase activity, ceruloplasmin and related parameters in rats ingesting lead acetate. In: Hemphill DD (ed) Trace substances in environmental health, vol 18. University of Mussouri Press, Columbia, pp 497–504

    Google Scholar 

  • Nichols DM, McLachlan DRXC (1990) Issues of lead toxicity. In: Yasumura S (ed) In vivo body composition studies. Plenum Press, New York, pp 237–246

    Chapter  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Orhan IE (2012) Centella asiatica (L.): from traditional medicine to modern medicine with neuroprotective potential. Evid Based Complement Altern Med 2012:1–8

    Google Scholar 

  • Petit TL, Alfano DP, Leboutillier JC (1983) Early lead exposure and the hippocampus: a review and recent advances. Neurotoxicology 4:79–94

    CAS  Google Scholar 

  • Prasanthi RPJ, Devi CB, Basha RM, Reddy GR (2010) Calcium and zinc supplementation protects lead (Pb)-induced perturbations in antioxidant enzymes and lipid peroxidation in developing mouse brain. Int J Dev Neurosci 28:161–167

    Article  CAS  Google Scholar 

  • Ramana KD, Singhal SS, Reddy AB (2014) Therapeutic potential of natural pharmacological agents in the treatment of human diseases. BioMed Res Int 1–4, Article ID 573452

  • Rao KGM, Rao MS, Rao SG (2005) Centella asiatica (Linn) induced behavioural changes during growth spurt period in neonatal rats. Neuroanatomy 4:18–23

    Google Scholar 

  • Reckziegel P, Dias VT, Benvegnu D, Boufleur N, Barcelos RCS, Segat HJ, Pase CS, Dos Santos CMM, Flore EMM, Burger ME (2011) Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment. Toxicol Lett 203:74–81

    Article  CAS  Google Scholar 

  • Reddy GR, Basha MR, Devi CB, Suresh A, Baker JL, Shafeek A, Heinz J, Chetty S (2003) Lead induced effects on acetylcholinesterase activity in cerebellum and hippocampus of developing rat. Int J Dev Neurosci 21:347–352.

  • Reshma Anjum M, Reddy PS (2013) Effect of perinatal exposure to lead acetate on testicular lipid peroxidation adult rats. Int J Pharm Bio Sci 4:893–898

    CAS  Google Scholar 

  • Rodrigues ALS, Rocha MA, Souza DA, Mello CF (1996) Effect of perinatal lead exposure on rat behaviour in open field and two way avoidance tasks. Pharmacol Toxicol 79:150–156

    Article  CAS  Google Scholar 

  • Ronis MJ, Badger TM, Robertson PK, Sheikh F (1996) Reproductive toxicity and growth effects in rats exposed to lead at different periods during development. Toxicol Appl Pharmacol 136:361–371

    Article  CAS  Google Scholar 

  • Ryzhavskii B, Lebedko OA, Belolyubskaya DS, Baranova SN (2008) Long-term consequences of prenatal exposure to lead on brain development in rats. Neurosci Behav Physiol 38:145–148

    Article  CAS  Google Scholar 

  • Sandhir R, Julka D, Gill KD (1994) Lipoperoxidative damage on lead treatment in rat brain and its implications on membrane bound enzymes. Pharmacol Toxicol 74:66–71

    Article  CAS  Google Scholar 

  • Sansar W, Gamrani H (2003) The pharmacological effect of Artemisia absinthium extract in protecting adult rats against lead neurotoxicity. J Neurol Sci 333:e598

    Article  Google Scholar 

  • Shih TM, Hanin I (1978) Effects of chronic lead exposure on levels of acetylcholine and choline and on acetylcholine turnover rate in rat brain areas in vivo. Psychopharmacology 58:263–269

    Article  CAS  Google Scholar 

  • Shinomol GK, Muralidhara K (2008) Effect of Centella asiatica leaf powder on oxidative markers in brain regions of prepubertal mice in vivo and it’s in vitro efficacy to ameliorate 3-NPA-induced oxidative stress in mitochondria. Phytomedicine 15:971–984

    Article  Google Scholar 

  • Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN (1999) In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol 65:1–11

    Article  CAS  Google Scholar 

  • Sivaprasad R, Nagaraj M, Varalakshmi P (2002) Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney. Arch Toxicol 76:437–441

    Article  CAS  Google Scholar 

  • Sivaprasad R, Nagaraj M, Varalakshmi P (2004) Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver. J Nutr Biochem 15:18–23

    Article  CAS  Google Scholar 

  • Sugunabai J, Jeyaraj M, Karpagam T (2015) Analysis of functional compounds and antioxidant activity of Centella asiatica. World J Pharm Pharmceu Sci 4:1982–1993

    CAS  Google Scholar 

  • Sun L, Zhao ZY, Hu J, Zhou XL (2005) Potential association of lead exposure during early development of mice with alteration of hippocampus nitric oxide levels and learning memory. Biomed Environ Sci 18:375–378

    CAS  Google Scholar 

  • Veerendra Kumar MH, Gupta YK (2003) Effect of Centella asiatica on cognition and oxidative stress in an intra-cerebroventricular streptozotocin model of Alzheimer’s disease in rats. Clin Exp Pharmacol Physiol 30:336–342

    Article  CAS  Google Scholar 

  • Verina T, Rohde CA, Guilarte TR (2007) Environmental Pb2+ exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. Neuroscience 145:1037–1047

    Article  CAS  Google Scholar 

  • Wang XS, Dong Q, Zuo JP, Fang N (2003) Structure and potential immunological activity of a pectin from Centella asiatica (L.) Urban. Carbohydr Res 338:2393–2402

    Article  CAS  Google Scholar 

  • Wijeweera P, Arnason JHT, Koszycki D, Merali Z (2006) Evaluation of anxiolytic properties of gotukola (Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine 13:668–676

    Article  CAS  Google Scholar 

  • Williams K, Wilson MA, Bressler J (2000) Regulation and developmental expression of the divalent metal ion transporter in the rat brain. Cell Mol Biol 46:563–571

    CAS  Google Scholar 

  • Xu MF, Xiong YY, Liu JK, Qian JJ, Zhu L, Gao J (2012a) Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharm Sin 33:578–587

    Article  CAS  Google Scholar 

  • Xu CL, Wang QZ, Sun LM, Li XM, Deng JM, Li LF, Zhang J, Xu R, Ma PS (2012b) Asiaticoside: attenuation of neurotoxicity induced by MPTP in a rat model of Parkinsonism via maintaining redox balance and upregulating the ratio of Bcl-2/Bax. Pharmacol Biochem Behav 100:413–418

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank Dr. K.V.S. Sarma, Professor (Statistics), S.V. University, Tirupati, for providing assistance in the statistical analysis. KPR and CHS are grateful to the University Grants Commission, New Delhi, for financial support in the form of UGC-BSR (RFMS) fellowships.

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Author notes

  1. Swetha Chintapanti and K. Pratap Reddy contributed equally for this work

Authors and Affiliations

  1. Department of Biotechnology, Sri Venkateswara University, Tirupati, 517502, India

    Swetha Chintapanti & K. Pratap Reddy

  2. Department of Zoology, Sri Venkateswara University, Tirupati, 517502, India

    Swetha Chintapanti, K. Pratap Reddy & P. Sreenivasula Reddy

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  1. Swetha Chintapanti
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  2. K. Pratap Reddy
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  3. P. Sreenivasula Reddy
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Contributions

PSR conceived the idea, provided facilities, and supervised the work. KPR maintained rat colony and treatments and performed behavioral studies and assayed AChE activity. CHS prepared CA extract, analyzed the extract, and determined the Pb levels. KPR prepared rough draft of manuscript and all the authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to P. Sreenivasula Reddy.

Ethics declarations

All experimental investigations were done in compliance with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals, Government of India (CPCSEA 2003). The protocol was approved by the Institutional Animal Ethics Committee (Regd. No. 438/01/a/CPCSEA/dt.17.07.2001) in its resolution no: 57/2012/(i)/a/CPCSEA/IAEC/SVU/ PSR-KPR dt.08-07-2012. The study was planned and organized as completely double blind.

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The authors declare that they have no conflicts of interest.

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Responsible editor: Philippe Garrigues

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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 25, 13173–13185 (2018). https://doi.org/10.1007/s11356-018-1500-x

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