Skip to main content

Protective Effect of Bacopa monniera on Methyl Mercury-Induced Oxidative Stress in Cerebellum of Rats

Abstract

Methyl mercury (MeHg) is a ubiquitous environmental pollutant leading to neurological and developmental deficits in animals and human beings. Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in Ayurveda, a traditional medicine system in India. The objective of the present study was to investigate whether Bacopa monniera extract (BME) could potentially inhibit MeHg-induced toxicity in the cerebellum of rat brain. 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) for 21 days. After the treatment period, we observed that MeHg exposure significantly inhibited the activities of superoxide dismutase, catalase, glutathione peroxidase, and increased the glutathione reductase activity in cerebellum. It was also found that the level of thiobarbituric acid-reactive substances was increased with the concomitant decrease in the glutathione level in MeHg-induced rats. These alterations were prevented by the administration of BME. Behavioral interference in the MeHg-exposed animals was evident through a marked deficit in the motor performance in the rotarod task, which was completely recovered to control the levels by BME administration. The total mercury content in the cerebellum of MeHg-induced rats was also increased which was measured by atomic absorption spectrometry. The levels of NO2 and NO3 in the serum were found to be significantly increased in the MeHg-induced rats, whereas treatment with BME significantly decreased their levels in serum to near normal when compared to MeHg-induced rats. These findings strongly implicate that BM has potential to protect brain from oxidative damage resulting from MeHg-induced neurotoxicity in rat.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    PubMed  Article  CAS  Google Scholar 

  • Aschner M, Yao CP, Allen JW, Tan KH (2000) Methylmercury alters glutamate transport in astrocytes. Neurochem Int 37:199–206

    PubMed  Article  CAS  Google Scholar 

  • Aschner M, Syversen T, Souza DO, Rocha JB, Farina M (2007) Involvement of glutamate and reactive oxygen species in methyl mercury neurotoxicity. Braz J Med Biol Res 40:285–291

    PubMed  Article  CAS  Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    PubMed  Article  CAS  Google Scholar 

  • Bhattacharya SK, Kumar A, Ghosal S (1999) Effect of Bacopa monniera on animal models of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats. Res Commun Pharmacol Toxicol 4:1–12

    Google Scholar 

  • Bhattacharya SK, Bhattacharya A, Kumar A, Ghosal S (2000) Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus. Phytother Res 14:174–179

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC (2002) Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res 16:639–664

    PubMed  Article  CAS  Google Scholar 

  • Clarkson TW, Magos L, Myers GJ (2003) The toxicology of mercury current exposures and clinical manifestations. N Engl J Med 349:1731–1737

    PubMed  Article  CAS  Google Scholar 

  • Dawson VL, Dawson TM, London ED, Bredt DS, Snyder SH (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 88:6368–6371

    PubMed  Article  CAS  Google Scholar 

  • Duham NW, Miya TS (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc 46:208–209

    Google Scholar 

  • Ernst E (2006) Herbal remedies for anxiety—a systematic review of controlled clinical trials. Phytomedicine 13:205–208

    PubMed  Article  CAS  Google Scholar 

  • Farina M, Dahm KC, Schwalm FD et al (2003) Methylmercury increases glutamate release from brain synaptosomes and glutamate uptake by cortical slices from suckling rat pups:modulatory effect of ebselen. Toxicol Sci 73:135–140

    PubMed  Article  CAS  Google Scholar 

  • Farina M, Franco JL, Ribas CM, Meotti FC, Missau FC, Pizzolatti MG, Dafre AL, Antos ARS (2005) Protective effects of Polygala paniculata extract against methyl mercury induced neurotoxicity in mice. J Pharm Pharmacol 57:1503–1508

    PubMed  Article  CAS  Google Scholar 

  • Franco JL, Teixeira A, Meotti FC, Ribas CM, Stringari J, Garcia Pomblum SC, Moro AM, Bohrer D, Bairros AV, Dafre AL, Santos ARS, Farina M (2006) Cerebellar thiol status and motor deficit after lactational exposure to methylmercury. Environ Res 102:22–28

    PubMed  Article  CAS  Google Scholar 

  • 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 101:127–131

    Article  Google Scholar 

  • Gul M, Kutay FZ, Temocin S, Hanninen O (2000) Cellular and clinical implications of glutathione. Indian J Exp Biol 38:625–634

    PubMed  CAS  Google Scholar 

  • Hunter D, Russell DS (1954) Focal cerebral and cerebellar atrophy in a human subject due to organic mercury compounds. J Neurol Neurosurg Psychiat 17:235–241

    PubMed  Article  CAS  Google Scholar 

  • Hunter D, Bomford RR, Russell DS (1940) Poisoning by methylmercury compounds. Quart J Med 9:193–213

    CAS  Google Scholar 

  • Ikeda M, Komachi H, Sato I, Himi T, Yuasa T, Murota S (1999) Induction of neuronal nitric oxide synthase by methylmercury in the cerebellum. J Neurosci Res 55:352–356

    PubMed  Article  CAS  Google Scholar 

  • Juarez BI, Martinez ML, Montante M, Dufour L, Garcia E, Jimenez-Capdeville ME (2002) Methylmercury increases glutamate extracellular levels in frontal cortex of awake rats. Neurotoxicol Teratol 24:767–771

    PubMed  Article  CAS  Google Scholar 

  • Juarez BI, Portillo-Salazar H, Gonzalez-Amaro R, Mandeville P, Aguirre JR, Jimenez ME (2005) Participation of N-methyl d-aspartate receptors on methylmercury-induced DNA damage in rat frontal cortex. Toxicology 207:223–229

    PubMed  Article  CAS  Google Scholar 

  • Kim CY, Watanabe C, Kasanuma Y, Satoh H (1995) Inhibition of glutamyl transpeptidase decreases renal deposition of mercury after mercury vapour exposure. Arch Toxicol 69:722–724

    PubMed  Article  CAS  Google Scholar 

  • 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 191:241–246

    Article  CAS  Google Scholar 

  • Kishore K, Singh M (2005) Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (Brahmi), on experimental amnesia in mice. Indian J Exp Biol 43:640–645

    PubMed  Google Scholar 

  • Lash LH, Zarups RK (1996) Alterations in renal cellular glutathione metabolism after in vivo administration of a sub toxic dose of mercuric chloride. J Biochem Toxicol 11:1–9

    PubMed  Article  CAS  Google Scholar 

  • Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    PubMed  Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the follin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Manfroi CB, Schwalm FD, Cereser V, Abreu F, Oliveira A, Bizarro L, Rocha JB, Frizzo ME, Souza DO, Farina M (2004) Maternal milk as methylmercury source for suckling mice: neurotoxic effects involved with the cerebellar glutamatergic system. Toxicol Sci 81:172–178

    PubMed  Article  CAS  Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    PubMed  Article  CAS  Google Scholar 

  • 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 458:215–218

    PubMed  Article  CAS  Google Scholar 

  • Moron M, Depierre JW, Mannervik BT (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78

    PubMed  Article  CAS  Google Scholar 

  • Moskaug JO, Carlson H, Myhrstad MC, Blomhoff R (2005) Polyphenols and glutathione synthesis regulation. Am J Clin Nutr 81:277S–283S

    PubMed  CAS  Google Scholar 

  • Nagashima KA (1997) Review of experimental methylmercury toxicity in rats: neuropathology and evidence for apoptosis. Toxicol Pathol 25:624–631

    PubMed  Article  CAS  Google Scholar 

  • Nathan PJ, Clarke J, Lloyd J, Huchison CW, Downey L, Stough C (2001) The acute effects of an extract of Bacopa monnieri on cognitive function in healthy normal subjects. Hum Psychopharmacol 16:345–351

    PubMed  Article  Google Scholar 

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

    Article  Google Scholar 

  • Ou YC, White CC, Krejsa CM, Ponce RA, Kavanagh TJ, Faustman EM (1999) The role of intracellular glutathione in methylmercuryinduced toxicity in embryonic neuronal cells. Neurotoxicology 20:793–804

    PubMed  CAS  Google Scholar 

  • Parvinder K, Schulz K, Aschner M, Syversen T (2007) Role of docosahexaenoic acid in modulating methylmercury-induced neurotoxicity. Toxicol Sci 100(2):423–432

    Article  Google Scholar 

  • Passos CJS, Sampaio DS, Lemire M, Fillion M, Guimaraes JRD, Lucotte M, Mergler D (2008) Daily mercury intake in fish eating populations in the Brazilian Amazon. Exp Sci Environ Epidemiol 18:76–87

    Article  CAS  Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in sterotaxic coordinates. Academic Press, New York

    Google Scholar 

  • Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J (2002) Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 27:279–281

    PubMed  Article  Google Scholar 

  • Rosen DR (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 364:362

    PubMed  CAS  Google Scholar 

  • Rotruck JT, Popa AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstar WG (1973) Selenium: biochemical role as a component of GPx. Science 179:588–590

    PubMed  Article  CAS  Google Scholar 

  • Russo A, Borrelli F (2005) Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine 12:305–317

    PubMed  Article  CAS  Google Scholar 

  • Russo A, Izzo AA, Borrelli F, Renis M, Vanella A (2003) Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damage. Phytother Res 17:870–875

    PubMed  Article  Google Scholar 

  • Sairam K, Rao CV, Goel RK (2001) Prophylactic and curative effects of Bacopa monniera in gastric ulcer models. Phytomedicine 8:423–430

    PubMed  Article  CAS  Google Scholar 

  • Saraf MK, Prabhakar S, Pandhi P, Anand A (2008) Bacopa monnieri ameliorates amnesic effects of diazepam qualifying behavioral–molecular partitioning. Neuroscience 155:476–484

    PubMed  Article  CAS  Google Scholar 

  • Shanker G, Singh HK (2000) Anxiolytic profile of standardized Brahmi extract. Indian J Pharmacol 32:152

    Google Scholar 

  • Sharma R, Chaturvedi C, Tewari PV (1987) Efficacy of Bacopa monniera in revitalizing intellectual functions in children. J Res Edu Ind Med 1:12

    Google Scholar 

  • Shinyashiki M, Kumagai Y, Nakajima H, Nagafune J, 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 798:147–155

    PubMed  Article  CAS  Google Scholar 

  • Singh HK, Dhawan BN (1982) Effect of Bacopa monniera Linn. (Brahmi) extract on avoidance responses in rat. J Ethnopharmacol 5:205–214

    PubMed  Article  CAS  Google Scholar 

  • Singh HK, Dhawan BN (1997) Neuropsychopharmacological effects of the ayurvedic nootropic Bacopa monniera Linn (Brahmi). Indian J Pharmacol 29:359–365

    Google Scholar 

  • Singh HK, Rastogi RP, Srimal RC, Dhawan BN (1988) Effects of bacosides A and B on avoidance response in rats. Phytother Res 2:70–75

    Article  CAS  Google Scholar 

  • Sirois JE, Atchison WD (2000) Methylmercury affects multiple subtypes of calcium channels in rat cerebellar granule cells. Toxicol Appl Pharmacol 167:1–11

    PubMed  Article  CAS  Google Scholar 

  • Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ (2001) The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berlin) 156:481–484

    Article  CAS  Google Scholar 

  • Stringari J, Meotti FC, Souza DO, Santos ARS, Farina M (2006) Postnatal methylmercury exposure induces hyperlocomotor activity and cerebellar oxidative stress in mice: dependence on the neurodevelopmental period. Neurochem Res 31:563–569

    PubMed  Article  CAS  Google Scholar 

  • Sumathy T, Subramanian S, Govindaswamy S, Balakrihna K, Veluchany G (2001) Protective role of Bacopa monnieri on morphine induced hepatotoxicity in rats. Phytother Res 15:643–645

    PubMed  Article  CAS  Google Scholar 

  • Takeuchi T (1968) Pathology of minamata disease. In: Kutsuna M (ed) Study group of minamata disease. Kumamoto University, Shuhan Publisher, Tokyo, pp 141–228

    Google Scholar 

  • Takeuchi T (1982) Pathology of minamata disease. With special reference to its pathogenesis. Acta Pathol Jpn 32(1):73–99

    PubMed  Google Scholar 

  • Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D (2003) Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol 18:149–175

    PubMed  Article  CAS  Google Scholar 

  • Tripathi YB, Chaurasia S, Tripathi E, Upadhyay A, Dubey GP (1996) Bacopa monniera Linn. as an antioxidant: mechanism of action. Indian J Exp Biol 34:523–526

    PubMed  CAS  Google Scholar 

  • Vohora D, Pal SN, Pillai KK (2000) Protection from phenytoin induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant. J Ethnopharmacol 71:383–390

    PubMed  Article  CAS  Google Scholar 

  • Vollala VR, Upadhya S, Nayak S (2010) Effect of Bacopa monniera Linn. (Brahmi) extract on learning and memory in rats: a behavioural study. J Vet Behav 5:69–74

    Article  Google Scholar 

  • 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 175:107–110

    PubMed  Article  CAS  Google Scholar 

  • Yamashita T, Ando Y, Nakamura M, Obayashi K, Terazaki H, Haraoka K, Guo SX, Ueda M, Uchino M (2004) Inhibitory effect of α-tocopherol on methylmercury-induced oxidative stress. Environ Health Prev Med 9:111–117

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

The work described in this article was supported by Department of Medical Biochemistry, DR. ALMPGIBMS, University of Madras, Taramani Campus, Chennai 113, Tamil Nadu, India.

Conflict of interest

The authors declare that there is no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thangarajan Sumathi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sumathi, T., Shobana, C., Christinal, J. et al. Protective Effect of Bacopa monniera on Methyl Mercury-Induced Oxidative Stress in Cerebellum of Rats. Cell Mol Neurobiol 32, 979–987 (2012). https://doi.org/10.1007/s10571-012-9813-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-012-9813-7

Keywords

  • Methyl mercury
  • Bacopa monniera
  • Cerebellum
  • Neuroprotection