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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2015

Open Access 01-12-2015 | Research article

Neuroprotective effect of Tagara, an Ayurvedic drug against methyl mercury induced oxidative stress using rat brain mitochondrial fractions

Authors: Dhanoop Manikoth Ayyathan, Rajasekaran Chandrasekaran, Kalaivani Thiagarajan

Published in: BMC Complementary Medicine and Therapies | Issue 1/2015

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Abstract

Background

Methyl mercury (MeHg), an important environmental toxicant is implicated in neurological disorders such as Hunter-Russell syndrome and Autism. Therefore, the present work is in search of new drugs that can alleviate MeHg toxicity. In this connection, Tagara, an ayurvedic drug is used for assessing its neuro protective effect against MeHg toxicity.

Methods

In the present study, we assessed the phytochemical contents of Tagara by colorimetric and HPLC analyses. The neuroprotective effect of Tagara on MeHg induced neurotoxicity was measured in terms of viability by MTT assay and oxidative stress in terms of catalase activity, glutathione and thiobarbituric acid reactive substance levels. Further, the chelating effect of Tagara towards MeHg was performed to identify the molecular mechanism. Statistical analysis was done by statistical package for social sciences (SPSS) version 16.0.

Results

The results demonstrated that Tagara contains significant amounts of phenols and flavonoids. Also, HPLC analysis of Tagara revealed the presence of essential oils such as hydroxyvalerenic and valerenic acids. Our results demonstrated that exposure of rat brain mitochondrial fractions to MeHg resulted in a dose dependent death in MTT assay and IC50 value was found to be 10 μM. However, a 250 μg dose of Tagara effectively prevented MeHg induced mitochondrial damage. The oxidative stress caused by MeHg results in elevated levels of reactive oxygen species as evidenced by elevated TBARS (Thiobarbituric acid-reactive substances) levels and diminished catalase enzyme activity and glutathione content. However, Tagara at 250 μg concentration offsets these alterations caused by MeHg. Further, Tagara also diminished GSH oxidation caused by MeHg, confirming its chelating effect, one of the molecular mechanisms that triggers protection against oxidative damage.

Conclusion

Our results revealed that MeHg induced toxicity is predominantly mediated through oxidative stress mechanism and the propensity of Tagara to abolish such reactions. Hence, we propose that Tagara with a source of potential neuroprotectants may be a useful approach to alleviate MeHg associated neurotoxicity.
Literature
1.
Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006;36:609–62.CrossRefPubMed
2.
Liu W, Xu Z, Deng Y, Xu B, Wei Y, Yang T. Protective effects of memantine against methylmercury-induced glutamate dyshomeostasis and oxidative stress in rat cerebral cortex. Neurotox Res. 2013;24:320–37.CrossRefPubMed
3.
Debes F, Budtz-Jorgensen E, Weihe P, White RF, Grandjean P. Impact of prenatal methylmercury exposure on neurobehavioral function at age 14 years. Neurotoxicol Teratol. 2006;28(5):536–47.CrossRefPubMed
4.
Aschner M, Syversen T, Souza DO, Rocha JB, Farina M. Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. Braz J Med Biol Res. 2007;40:285–91.CrossRefPubMed
5.
Ceccatelli S, Daré E, Moors M. Methylmercury-induced neurotoxicity and apoptosis. Chem Biol Interact. 2010;188:301–8.CrossRefPubMed
6.
Farina M, Rocha JBT, Aschner A. Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies. Life Sci. 2011;89(15–16):555–63.CrossRefPubMedPubMedCentral
7.
8.
Farina M, Avila DS, da Rocha JBT, Aschner M. Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int. 2013;62:575–94.CrossRefPubMed
9.
10.
Morazzoni P, Bombardelli E. Valeriana officinalis: traditional use and recent evaluation of activity. Fitoterapia. 1995;66:99–112.
11.
Sangeeta PS, Chandra SM, Kanwaljit C. Involvement of nitric oxide (NO) signalling pathway in the antidepressant activity of essential oil of Valeriana wallichii Patchouli alcohol chemotype. Phytomedicine. 2011;18:1269–75.CrossRef
12.
Shalam M, Shantakumar SM, Narasu ML. Pharmacological and biochemical evidence for the antidepressant effect of the herbal preparation Trans-01. Indian J Pharmacol. 2007;39:231–4.CrossRef
13.
Agrawal A. A comparative study of psychotropic drugs and bio-feedback therapy in the prevention and management of psychosomatic disorder, PhD thesis. Varanasi: Banaras Hindu University; 1993.
14.
Kujala TS, Loponen JM, Klika KD, Pihlaja K. Phenolics and betacyanins in red beetroot (Beta vulgaris) root: distribution and effect of cold storage on the content of total phenolics and three individual compounds. J Agric Food Chem. 2000;48:5338–42.CrossRefPubMed
15.
Nieva MMI, Isla MI, Sampitro AR, Vattuone MA. Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. J Ethnopharmacol. 2000;109:114.
16.
Roy UH. Valerian root, Valeriana officinalis, analytical, quality control and therapeutic monograph. American Herbal Pharmacopoeia. 1999;1–25.
17.
Jeferson LF, Hugo CB, James S, Fabiana CM, Thais P, Beatriz GM, et al. Mercurial-induced hydrogen peroxide generation in mouse brain mitochondria: protective effects of quercetin. Chem Res Toxicol. 2007;20:1919–26.CrossRef
18.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265.PubMed
19.
InSug O, Datar S, Koch CJ, Shapiro IM, Shenker BJ. Mercuric compounds inhibit human monocyte function by inducing apoptosis: evidence for formation of reactive oxygen species, development of mitochondrial membrane permeability transition and loss of reductive reserve. Toxicology. 1997;124:211–24.CrossRefPubMed
20.
21.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–8.CrossRefPubMed
22.
23.
Kalia K, Flora SJS. Strategies for safe and effective treatment for chronic arsenic and lead poisoning. J Occup Hlth. 2005;47:1–21.CrossRef
24.
25.
Surajit S, Koushik R, Yogendra K, Shilpa G, Kauser H, Kumar S, et al. Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats. Phytomedicine. 2012;19:924–9.CrossRef
26.
Aschner M, Syversen T. Methylmercury: recent advances in the understanding of its neurotoxicity. Ther Drug Monit. 2005;27:278–83.CrossRefPubMed
27.
Poli G, Leonarduzzi G, Biasi F, Chiarpotto E. Oxidative stress and cell signalling. Curr Med Chem. 2004;11:1163–82.CrossRefPubMed
28.
Graziano JH, Lolacono NJ, Moulton T, Mitchell ME, Slavkovich V, Zarate C. Controlled study of meso-2, 3-dimercaptosuccinic acid for the management of childhood lead intoxication. J Pediatr. 1992;120:133–9.CrossRefPubMed
29.
Hucklenbroich J, Klein R, Neumaier B, Graf R, Fink GR, Schroeter M, et al. Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Research & Therapy. 2014;5:100.CrossRef
30.
Shanker G, Aschner M. Identification and characterization of uptake systems for cystine and cysteine in cultured astrocytes and neurons: evidence for methylmercury-targeted disruption of astrocyte transport. J Neurosci Res. 2001;66:998–1002.CrossRefPubMed
31.
Allen JW, Shanker G, Tan KH, Aschner M. The consequences of methylmer-cury exposure on interactive functions between astrocytes and neurons. Neurotoxicology. 2002;23:755–9.CrossRefPubMed
32.
Shanker G, Syversen T, Aschner JL, Aschner M. Modulatory effect of glu-tathione status and antioxidants on methylmercury-induced free radical formation in primary cultures of cerebral astrocytes. Brain Res Mol Brain Res. 2005;137:11–22.CrossRefPubMed
33.
Sumi D. Biological effects of and responses to exposure to electrophilic environmental chemicals. J Health Science. 2008;54:6.CrossRef
34.
Heggland I, Kaur P, Syversen T. Uptake and efflux of methyl mercury in vitro: comparison of transport mechanisms in C6, B35 and RBE4 cells. Toxicol In Vitro. 2009;23:1020–7.CrossRefPubMed
35.
Ayyathan DM, Chandrasekaran R, Thiagarajan K. Neuroprotective effect of Brahmi, an ayurvedic drug against oxidative stress induced by methyl mercury toxicity in rat brain mitochondrial-enriched fractions. Nat Prod Res. 2015;29(11):1046.CrossRefPubMed
36.
Yamashita T, Ando Y, Nakamura M, Obayashi K, Terazaki H, Haraoka K, et al. Inhibitory effect of α-tocopherol on methylmercury-induced oxidative stress. Environ Health Prev Med. 2004;9:111–7.CrossRefPubMedPubMedCentral
Metadata
Title
Neuroprotective effect of Tagara, an Ayurvedic drug against methyl mercury induced oxidative stress using rat brain mitochondrial fractions
Authors
Dhanoop Manikoth Ayyathan
Rajasekaran Chandrasekaran
Kalaivani Thiagarajan
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2015
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-015-0793-2

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