期刊论文详细信息
BMC Complementary and Alternative Medicine
Neuroprotective effect of Tagara, an Ayurvedic drug against methyl mercury induced oxidative stress using rat brain mitochondrial fractions
Kalaivani Thiagarajan1  Rajasekaran Chandrasekaran1  Dhanoop Manikoth Ayyathan1 
[1] School of Biosciences and Technology, VIT University, Tamilnadu, India
关键词: Neuroprotection;    Mitochondrial viability;    Tagara;    Oxidative stress;    Methyl mercury;   
Others  :  1222571
DOI  :  10.1186/s12906-015-0793-2
 received in 2014-06-26, accepted in 2015-07-22,  发布年份 2015
PDF
【 摘 要 】

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 IC 50value 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.

【 授权许可】

   
2015 Ayyathan et al.

【 预 览 】
附件列表
Files Size Format View
20150823053642964.pdf 1933KB PDF download
Fig. 6. 54KB Image download
Fig. 5. 65KB Image download
Fig. 4. 66KB Image download
Fig. 3. 51KB Image download
Fig. 2. 25KB Image download
20150919112300545.pdf 861KB PDF download
【 图 表 】

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

【 参考文献 】
  • [1]Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006; 36:609-662.
  • [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; 24:320-337.
  • [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.
  • [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; 40:285-291.
  • [5]Ceccatelli S, Daré E, Moors M. Methylmercury-induced neurotoxicity and apoptosis. Chem Biol Interact. 2010; 188:301-308.
  • [6]Farina M, Rocha JBT, Aschner A. Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies. Life Sci. 2011; 89(15–16):555-563.
  • [7]Xu F, Farkas S, Kortbeek S, Zhang FX, Chen L, Zamponi GW, Syed NI. Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-D-Aspartate receptors. Molecular Brain. 2012; 5:30. BioMed Central Full Text
  • [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; 62:575-594.
  • [9]Shankar A. Ayurveda for neurological disorders. J Homeop Ayurv Med. 2013; 2:130.
  • [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; 18:1269-1275.
  • [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; 39:231-234.
  • [13]Agrawal A. A comparative study of psychotropic drugs and bio-feedback therapy in the prevention and management of psychosomatic disorder. Banaras Hindu University, Varanasi; 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.
  • [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, Rodrigo BL, Adair RSS, Alcir LD, Moacir GP, Marcelo F. Mercurial-induced hydrogen peroxide generation in mouse brain mitochondria: protective effects of quercetin. Chem Res Toxicol. 2007; 20:1919-1926.
  • [18]Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193:265.
  • [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; 124:211-224.
  • [20]Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82:70-77.
  • [21]Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95:351-358.
  • [22]Sinha AK. Colorimetric assay of catalase. Anal Brochem. 1972; 47:389-394.
  • [23]Kalia K, Flora SJS. Strategies for safe and effective treatment for chronic arsenic and lead poisoning. J Occup Hlth. 2005; 47:1-21.
  • [24]Flora SJS. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid Med Cell Longev. 2009; 2(4):191-206.
  • [25]Surajit S, Koushik R, Yogendra K, Shilpa G, Kauser H, Kumar S, Mishra K, Panjwani U. Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats. Phytomedicine. 2012; 19:924-929.
  • [26]Aschner M, Syversen T. Methylmercury: recent advances in the understanding of its neurotoxicity. Ther Drug Monit. 2005; 27:278-283.
  • [27]Poli G, Leonarduzzi G, Biasi F, Chiarpotto E. Oxidative stress and cell signalling. Curr Med Chem. 2004; 11:1163-1182.
  • [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; 120:133-139.
  • [29]Hucklenbroich J, Klein R, Neumaier B, Graf R, Fink GR, Schroeter M, Rueger MA. Aromatic-turmerone induces neural stem cell proliferation in vitro and in vivo. Stem Cell Research & Therapy. 2014; 5:100. BioMed Central Full Text
  • [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.
  • [31]Allen JW, Shanker G, Tan KH, Aschner M. The consequences of methylmer-cury exposure on interactive functions between astrocytes and neurons. Neurotoxicology. 2002; 23:755-759.
  • [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.
  • [33]Sumi D. Biological effects of and responses to exposure to electrophilic environmental chemicals. J Health Science. 2008; 54:6.
  • [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; 23:1020-1027.
  • [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.
  • [36]Yamashita T, Ando Y, Nakamura M, Obayashi K, Terazaki H, Haraoka K, Guo SX, Ueda M, Uchino M. Inhibitory effect of α-tocopherol on methylmercury-induced oxidative stress. Environ Health Prev Med. 2004; 9:111-117.
  文献评价指标  
  下载次数:38次 浏览次数:11次