Biological Trace Element Research

, Volume 155, Issue 1, pp 56–64 | Cite as

Effect of Bacopa monniera Extract on Methylmercury-Induced Behavioral and Histopathological Changes in Rats

  • Johnson Christinal
  • Thangarajan SumathiEmail author


Methylmercury (MeHg) is a well-recognized environmental contaminant with established health risk to human beings by fish and marine mammal consumption. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. This study was aimed to evaluate the effect of B. monniera extract (BME) on MeHg-induced toxicity in rat cerebellum. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with BME (40 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After treatment period, MeHg exposure significantly decreases the body weight and also caused the following behavioral changes. Decrease tail flick response, longer immobility time, significant decrease in motor activity, and spatial short-term memory. BME pretreatment reverted the behavioral changes to normal. MeHg exposure decreases the DNA and RNA content in cerebellum and also caused some pathological changes in cerebellum. Pretreatment with BME restored all the changes to near normal. These findings suggest that BME has a potent efficacy to alleviate MeHg-induced toxicity in rat cerebellum.


Methylmercury Bacopa monniera Behavioral Cerebellum Histopathology 



The study was supported by Department of Medical Biochemistry, DR.ALMPGIBMS, University of Madras, Taramani Campus, Chennai 113, Tamil Nadu, India.


  1. 1.
    Clarkson TW, Magos L, Myers GJ (2003) The toxicology of mercury current exposures and clinical manifestation. Nengl J Med 349:1731–1737CrossRefGoogle Scholar
  2. 2.
    Kowmulainen H, Bondy SC (1987) Increased free intrasynaptosomal Ca2+ by neurotoxic organometals: distinctive mechanism. Toxicol Appl Pharmacol 88:77–86CrossRefGoogle Scholar
  3. 3.
    Marty MS, Atchison WD (1997) Pathways mediating Ca2+ entry in rat cerebellar granule cells following in vitro exposure to methylmercury. Toxicol Appl Pharmacol 147:319–330PubMedCrossRefGoogle Scholar
  4. 4.
    Kunimoto M (1994) Methylmercury induced apoptosis of rat cerebellar neurons in primary culture. Biochem Biophys Res Commun 204:310–314PubMedCrossRefGoogle Scholar
  5. 5.
    Nagashima K (1997) A review of experimental methylmercury toxicity in rats: neuropathology and evidence for apoptosis. Toxicol Pathol 25:624–631PubMedCrossRefGoogle Scholar
  6. 6.
    Aschner M, Yao CP, Allen JW, Tan KH (2000) Methylmercury alters glutamate transport in astrocytes. Neurochem Int 37:199–206PubMedCrossRefGoogle Scholar
  7. 7.
    Manfroi CB, Schwalm FD, Frizzo ME, Souza DO, Farina M (2004) Maternal milk as methylmercury source for sucking mice: neurotoxic effects involved with the cerebellar glutamatergic system. Toxicol Sci 81:172–178PubMedCrossRefGoogle Scholar
  8. 8.
    Ou YC, White CC, Krejsa CM, Ponce RA, Kavanagh TJ, Faustman EM (1999) The role of intracellular glutathione in Methylmercury induced toxicity in embryonic neuronal cells. Neurotoxicology 20:793–804PubMedGoogle Scholar
  9. 9.
    Chang LW (1980) In: Spencer PS, Schaumburg HH (eds) Experimental and clinical neurotoxicity. Williams & Willkins, Baltimore, Part I. Fundamental of Experimental and clinical neurotoxicity Part II - Chemicals with neurotoxic potential, pp 508–526Google Scholar
  10. 10.
    Hunter D, Bomford RR, Russell DS (1940) Poisoning by methylmercury compounds. Quart J Med 9:193–213Google Scholar
  11. 11.
    Hunter D, Russell DS (1954) Focal cerebral and cerebellar atrophy in a human subject due to organic mercury compounds. J Neurol Neurosurg Psychiat 17:235–241PubMedCrossRefGoogle Scholar
  12. 12.
    Takeuchi T (1968) Pathology of Minamata disease. In: Kutsuna M (ed) Study group of Minamata disease. Kumamoto University, Shuhan Publisher, Tokyo, pp 141–228Google Scholar
  13. 13.
    Takeuchi T (1982) Pathology of minamata disease. With special reference to its pathogenesis. Acta Pathol Jpn 32(1):73–99PubMedGoogle Scholar
  14. 14.
    Rosen DR (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62PubMedCrossRefGoogle Scholar
  15. 15.
    Yamashita T, Ando Y, Obayashi K, Terazaki H, Sakashita N, Uchida K, Ohama E, Ando M, Uchino M (2000) Oxidative injury is present in purkinje cells in patients with olivopontocerebellar atrophy. J Neurol Sci 175:107–110PubMedCrossRefGoogle Scholar
  16. 16.
    Bckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrate:implication for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624CrossRefGoogle Scholar
  17. 17.
    Ikeda M, Komachi H, Sato I, Himi T, Yuasa T, Murota S (1999) Induction of neuronal nitric acid oxide synthase by methylmercury in the cerebellum. J Neurosci Res 55:352–356PubMedCrossRefGoogle Scholar
  18. 18.
    Shinyashiki M, Kumagai Y, Nakajima H, Homma-Takeda S, Sagai M, Shimojo N (1998) Differential changes in rat brain nitric oxide synthase in vivo and in vitro by methylmercury. Brain Res 798:147–155PubMedCrossRefGoogle Scholar
  19. 19.
    Miura N, Kaneko S, Hosoya S, Furuchi T, Miura K, Kuge S, Naganuma A (1999) Overexpression of L-glutamine: D-fructose-6-phosphate amidotransferase provides resistance to methylmercury in Saccharomyces cerevisiae. FEBS Lett 458:215–218PubMedCrossRefGoogle Scholar
  20. 20.
    Gupta R, Flora SJ (2006) Effect of Centella asiatica on arsenic-induced oxidative stress and metal distribution in rats. J Appl Toxicol 26:213–222PubMedCrossRefGoogle Scholar
  21. 21.
    Franco JL, Braga HC, Stringari J, Missau F, Posser T, Mendes B, Leal RB, Santos ARS, Dafre AL, Pizzolatti MG, Farina M (2007) Mercurial-induced hydrogen peroxide generation in mouse brain mitochondria: protective effects of quercetin. Chem Res Toxicol 20:1919–1926PubMedCrossRefGoogle Scholar
  22. 22.
    Xu Y, Li G, Han C, Sun L, Zhao R, Cui S (2005) Protective effects of Hippophae rhamnoides L. juice on lead-induced neurotoxicity in mice. Biol Pharm Bull 28:490–494PubMedCrossRefGoogle Scholar
  23. 23.
    Sumathi T, Shobana C, Christinal J, Anusha C (2012) Protective effect of Bacopa monniera on methyl mercury-induced oxidative stress in cerebellum of rats. Cell Mol Neurobiol 32:979–987PubMedCrossRefGoogle Scholar
  24. 24.
    Tripathi YB, Chaurasia S, Tripathi E, Upadhyay D, Dubey GP (1996) Bacopa monniera Linn. As an antioxidant: mechanism of action. Indian J Exp Biol 34:523–526PubMedGoogle Scholar
  25. 25.
    Kishora K, Singh M (2005) Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (Bhrami), on experimental amnesia in mice. Indian J Exp Biol 43:640–645Google Scholar
  26. 26.
    Ernst E (2006) Herbal remedies for anxiety-a systematic review of controlled clinical trials. Phytomedicine 13:205–208PubMedCrossRefGoogle Scholar
  27. 27.
    Shanker G, Singh HK (2000) Anxiolytic profile of standardized Brahmi extract. Indian J Pharmacol 32:152Google Scholar
  28. 28.
    Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC (2002) Antistress effects of bacosides of Bacopa monniera: modulation of Hsp7. Expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res 16:639–664PubMedCrossRefGoogle Scholar
  29. 29.
    Singh HK, Dhawan BN (1982) Effect of Bacopa monniera. Linn. (Bhrami) extract on avoidance responses in rat. J Ethanopharmacol 5:205–214CrossRefGoogle Scholar
  30. 30.
    Saraf MK, Prabhakar S, Pandhi P, Anandh A (2008) Bacopa monniera ameliorates amnesic effects of diazepam qualifying behavioral molecular partitioning. Neuroscience 155:476–484PubMedCrossRefGoogle Scholar
  31. 31.
    Russo A, Borrelli F (2005) Bacopa monniera, a reputed nootrophic plant: an overview. Phytomedicine 12:305–317PubMedCrossRefGoogle Scholar
  32. 32.
    Garai S, Mahato SB, Ohtani K, Yamasaki K (1996) Dammarane type triterpenoid saponins from Bacopa monniera. Phytochemistry 42:815–820PubMedCrossRefGoogle Scholar
  33. 33.
    Singh HK, Rastogi RP, Srimal RC, Dhawan BN (1988) Effects of bacosides A and B on avoidance response in rats. Phytother Res 2:70–75CrossRefGoogle Scholar
  34. 34.
    Singh HK, Dhawan BN (1997) Neuropsychopharmacological effects of the ayurvedic nootropic Bacopa monniera Linn(Brahmi). Indian J Pharmacol 29:359–365Google Scholar
  35. 35.
    Nathan PJ, Clarke J, Lloyd J, Huchison CW, Downey L, Stough C (2001) The acute effects of an extract of Bacopa monniera on cognitive function in healthy normal subjects. Hum Psychopharmacol 16:345–351PubMedCrossRefGoogle Scholar
  36. 36.
    Stough C, Lloyd J, Clarke J, Downey L, Hutchison CW, Rodgers T, Nathan PJ (2001) The chronic effects of an Bacopa monniera(Bhrami) on cognitive function in healthy human subjects. Psychopharmacology 156:481–484PubMedCrossRefGoogle Scholar
  37. 37.
    Vohora D, Pal SN, Pillai KK (2000) Protection from phenytoin-induced cognitive deficit by Bacopa monniera a reputed Indian nootropic plant. J Ethanopharmacol 71(3):383–390CrossRefGoogle Scholar
  38. 38.
    Anbarasi K, Vani G, Balakrishna K, CS S d (2006) Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sci 78:1378–1384PubMedCrossRefGoogle Scholar
  39. 39.
    Sumathi T, Nathiya VC, Sakthikumar M (2011) Protective effect of Bacoside-A against morphine induced oxidative stress in rats. Indian J Pharm Sci 73(4):409–415PubMedGoogle Scholar
  40. 40.
    Kim CY, Nakai K, Kameo S, Kurokawa N, Liu ZM, Satoh H (2000) Protective effect of melatonin on methyl mercury induced mortality in mice. Tohuko j Exp Med 191:241–246CrossRefGoogle Scholar
  41. 41.
    Yamashita T, Ando Y, Nakamura M, Obayashi K, Terazaki H, Haraoka K, Guo SX, Ueda M, Uchino M (2004) Inhibitory effect of a-tocopherol on methylmercury-induced oxidative stress. Environ Health Prev Med 9:111–117PubMedCrossRefGoogle Scholar
  42. 42.
    Parvinder K, Schulz K, Aschner M, Syversen T (2007) Role of docosahexaenoic acid in modulating methylmercury-induced neurotoxicity. Toxicol Sci 100(2):423–432CrossRefGoogle Scholar
  43. 43.
    Greice MR, de Lucena S, Franco JL, Ribas CM, Azevedo MS, Meotti FC, Gadotti VM, Dafre AL, Santos AR, Farina M (2007) Cipura paludosa extract prevents methyl mercury-induced neurotoxicity in mice. Basic Clin Pharmacol Toxicol 101:127–131CrossRefGoogle Scholar
  44. 44.
    Farina M, Franco JL, Ribas CM, Meotti FC, Missau FC, Pizzolatti MG, Dafre AL, Antos ARS (2005) Protective effect of Polygala paniculata extract against methylmercury induced neurotoxicity in mice. J Pharm Pharmacol 57:1503–1508PubMedCrossRefGoogle Scholar
  45. 45.
    Paxinos G, Watson C (1982) The rat brain in sterotaxic coordinates. Academic, New YorkGoogle Scholar
  46. 46.
    Searcy DG, Macinnis AJ (1970) Hybridizatoin and renaturation of the nonrepetive DNA of higher organisms. Biochim Biophys Acta 209(2):574–577PubMedCrossRefGoogle Scholar
  47. 47.
    Burton K (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62(2):315–332PubMedGoogle Scholar
  48. 48.
    Dische Z (1955) Colour reaction of nucleic acid components. In: Chargaff E, Davidson JN (eds) The nucleic acids, vol 1. Academic, New York, pp 285–305Google Scholar
  49. 49.
    Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  50. 50.
    Steru I, Chermat R, Thierry B, Simon P (1985) The tail suspensions test: a new method for screening antidepressants in mice. Psychopharmacol 85:367–70CrossRefGoogle Scholar
  51. 51.
    Dalvi A, Lucki I (1999) Murine models of depression. Psychopharmacol 147:14–16CrossRefGoogle Scholar
  52. 52.
    Hara K, Satio Y, Kirihara Y, Yamada Y, Sakura S, Kosaka Y (1999) The interaction of antinociceptive effects of morphine and GABA receptor agonists within the rats spinal cord. Anesth Analga 89:422–427Google Scholar
  53. 53.
    Rosa AO, Lin J, Caliixto JB, Santos AR, Rodrigues AL (2003) Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice. Behav Brian Res 61:43–50Google Scholar
  54. 54.
    Gralewicz S, Wiaderna D, Tomas T, Rydzynski K (1997) Behavioral changes following 4-week inhalation exposure to pseudocumene(1,2,4-trimethylbenzene) in the rat. Neurotoxicol Teratol 19:327–333PubMedCrossRefGoogle Scholar
  55. 55.
    Jothi A, Sethi P, Sharma D (2007) Bacopa monniera prevents from aluminium toxicity in the cerebral cortex of rat brain. J Ethanopharmacol 111:56–62CrossRefGoogle Scholar
  56. 56.
    Auger N, Kofman O, Kosatsky T, Armstrong B (2005) Low-level methylmercury exposure as a risk factor for neurologic abnormalities in adults. Neurotoxicology 26:149–157PubMedCrossRefGoogle Scholar
  57. 57.
    Zahir F, Shamin J, Rizwi Haq SK, Khan RH (2005) Low dose mercury toxicity and human health. Environ Toxicol Pharmacol 20:351–360PubMedCrossRefGoogle Scholar
  58. 58.
    Dietrich MO, Mantese CE, Dos Anjos G, Souza DO, Farina M (2005) Motor impairment induced by oral exposure to methylmercury in adult mice. Environ Toxicol Pharmacol 19:169–175PubMedCrossRefGoogle Scholar
  59. 59.
    Fisher C, Fredrikson A, Eriksson P (2008) Coexposure of neonatal mice to a flame retardant PBDE 99(2, 2’, 4, 4’,5-pentabromodiphenyl ether) and methylmercury enhances developmental neurotoxic defects. Toxicol Sci 101(2):275–285CrossRefGoogle Scholar
  60. 60.
    Gralewicz S, Wiaderna D, Lutz P, Sitarek K (2009) Neurobehavioural functions in adult progeny of rat mothers exposed to methylmercury or 2,2′,4,4′,5,5′-hexachlorobiphenyl(PCB 153) alone or their combination during gestation and lactation. Int J Occup Med Environ Health 22(3):277–291PubMedCrossRefGoogle Scholar
  61. 61.
    Hodges H, Allen Y, Sinden J, Mitchell SN, Arendt T, Lantos PL, Gray JA (1991) The effects of cholinergic drugs and cholinergic-rich foetal neural transplants on alcohol-induced deficits in radial maze performance in rats. Behav Brain Res 43:7–28PubMedCrossRefGoogle Scholar
  62. 62.
    Sringari J, Meotti FC, Souza DO, Santos AR, Farina M (2006) Postnatal methylmercury exposure induces hyperlocomotor activity and cerebellar oxidative stress in mice: dependence on the neurodevelopmental period. Neurochem Res 31:563–569CrossRefGoogle Scholar
  63. 63.
    Roegge CS, Morris JR, Villareal S, Wang VC, Powers BE, Klintsova AY, Greenough WT, Pessah IN, Schantz SL (2006) Purkinje cell and cerebellar effects following developmental exposure to PCBs and/or MeHg. Neurotoxicol Teratol 28:74–85PubMedCrossRefGoogle Scholar
  64. 64.
    Chuu JJ, Liu SH, Shiau SYL (2007) Differential neurotoxic effects of methylmercury and mercuric sulphide in rats. Toxicol Lett 169:109–120PubMedCrossRefGoogle Scholar
  65. 65.
    Nabi S, Ara A, Rizvi SJ (2012) Effect of methylmercury on depression like behavior in rats: a study mitigated by exogenous vitamins. Iran J Pharmacol Ther 11(1):1–5Google Scholar
  66. 66.
    Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepresent activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29:571–625PubMedCrossRefGoogle Scholar
  67. 67.
    Weingartner H, Silberman E (1982) Models of cognitive impairment: cognitive changes in depression. Psychopharmacol Bull 18:27–42PubMedGoogle Scholar
  68. 68.
    Eto K, Yasutake A, Miyamoto K, Tokunaga H, Otsuka Y (1997) Chronic effects of methylmercury in rats. II. Pathological aspects. Tohoku J Exp Med 182:197–205PubMedCrossRefGoogle Scholar
  69. 69.
    Nagashima K (1997) A review of experimental methylmercury toxicity in rats: neuropathology and evidence for apoptosis. Toxicol Pathol 25:624–630PubMedCrossRefGoogle Scholar
  70. 70.
    Eto K, Tokunaga H, Nagashima K, Takeuchi T (2002) An autopsy case of Minamata disease (methylmercury poisoning)—pathological viewpoints of peripheral nerves. Toxicol Pathol 30:714–722PubMedCrossRefGoogle Scholar
  71. 71.
    Chao ES, Gierthy JF, Frenkel GD (1984) A comparative study of the effects of mercury compounds on cell viability and nucleic acid synthesis in HeLa cells. Biochem Pharmacol 33(12):1941–1945PubMedCrossRefGoogle Scholar
  72. 72.
    Slotkin TA, Pachman S, Kavlock RJ, Bartolome J (1985) Effect of neonatal methylmercury exposure on development of nucleic acids and proteins in rat brain: egional specificity. Brain Res Bull 14(5):397–400PubMedCrossRefGoogle Scholar
  73. 73.
    Zahir F, Rizvi SJ, Haq SK, Khan RH (2006) Effect of methylmercury induced free radical stress on nucleic acids and protein: implications on cognitive and motor functions. Indian J Clin Biochem 21(2):149–152PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical SciencesUniversity of MadrasChennaiIndia

Personalised recommendations