Abstract
Domoic acid is a potent marine algal toxin produced by diatomic genus of Pseudo-nitzschia causing amnesic shell fish poisoning. Domoic acid toxicosis mainly involves excitotoxic effects coupled with oxidative stress. The present study was aimed to evaluate the protective effects of hydro-alcoholic extract of Terminalia arjuna (TA) against domoic acid induced toxic effects in Caco-2 cell line. It was observed that the toxicity induced by domoic acid in Caco-2 cells was mediated by oxidative insult leading to morphological changes, DNA damage and apoptosis. In our study pre-treatment of the cells with TA (10, 20 and 30 μg/ml) showed significant protection against domoic acid induced morphological, oxidative and apoptotic damages in a dose dependent manner. The effect of phytocompounds present in TA viz., kaempferol and arjungenin showed significant protection against domoic acid induced toxicity in Caco-2 cell line. Hence, it could be inferred that the protective effect of TA extract against domoic acid induced toxicity could be due to the individual or synergistic effects of kaempferol and argungenin. However, further clinical studies are warranted to consider TA as a natural remedy to prevent amnesic shell fish poisoning.
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Abbreviations
- TA:
-
Terminalia arjuna hydro-alcoholic extract
- MMP:
-
Mitochondrial membrane potential
- DAPI:
-
2-(4-amidinophenyl)-1H -indole-6-carboxamidine
- ROS:
-
Reactive oxygen species
- NO:
-
Nitric Oxide
- CAT:
-
Catalase
- GR:
-
Glutathione reductase
- ABTS:
-
2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)
References
Amira OC, Okubadejo NU (2007) Frequency of complementary and alternative medicine utilization in hypertensive patients attending an urban tertiary care centre in Nigeria. BMC Complement Altern Med 7(1):30
Ananth C, Thameem Dheen S, Gopalakrishnakone P, Kaur C (2001) Domoic acid-induced neuronal damage in the rat hippocampus: changes in apoptosis related genes (Bcl-2, Bax, caspase-3) and microglial response. J Neurosci Res 66:177–190
Berman FW, Murray TF (1997) Domoic acid neurotoxicity in cultured cerebellar granule neurons is mediated predominantly by NMDA receptors that are activated as a consequence of excitatory amino acid release. J Neurochem 69:693–703
Berman FW, LePage KT, Murray TF (2002) Domoic acid neurotoxicity in cultured cerebellar granule neurons is controlled preferentially by the NMDA receptor Ca 2 + influx pathway. Brain Res 924:20–29
Bortner CD, Cidlowski JA (1998) A necessary role for cell shrinkage in apoptosis. Biochem Pharmacol 56:1549–1559
Buttke TM, Sandstrom PA (1992) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10
Carvalho Pinto-Silva CR, Moukha S, Matias WG, Creppy EE (2008) Domoic acid induces direct DNA damage and apoptosis in Caco-2 cells: recent advances. Environ Toxicol 23:657–663
Choi EM (2011) Kaempferol protects MC3T3-E1 cells through antioxidant effect and regulation of mitochondrial function. Food Chem Toxicol 49:1800–1805
Das K, Chakraborty PP, Ghosh D, Nandi DK (2010) Protective effect of aqueous extract of Terminalia arjuna against dehydrating induced oxidative stress and uremia in male rat. Iran J Pharm Res 9:153–161
Dwivedi S (2007) Terminalia arjuna Wight Arn.—a useful drug for cardiovascular disorders. J Ethnopharmacol 114:114–129
Fotakis G, Timbrell JA (2006) In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 160:171–177
Ghosh J, Das J, Manna P, Sil PC (2010) Protective effect of the fruits of Terminalia arjuna against cadmium-induced oxidant stress and hepatic cell injury via MAPK activation and mitochondria dependent pathway. Food Chem 123:1062–1075
Giordano G, Klintworth HM, Kavanagh TJ, Costa LG (2008) Apoptosis induced by domoic acid in mouse cerebellar granule neurons involves activation of p38 and JNK MAP kinases. Neurochem Int 52:1100–1105
Hampson DR, Manalo JL (1998) The activation of glutamate receptors by kainic acid and domoic acid. Nat Toxins 6:153–158
Hasan MdK, Kabir AKL, Mistry S (2009) Chemical and biological investigation of leaves of polygonum plebeju. SJ Pharm Sci 2:71
Hong JT, Yen JH, Wang L, Lo YH, Chen ZT, Wu MJ (2009) Regulation of heme oxygenase-1 expression and MAPK pathways in response to kaempferol and rhamnocitrin in PC12 cells. Toxicol Appl Pharmacol 237:59–68
Jain S, Yadav PP, Gill V, Vasudeva N, Singla N (2009) Terminalia arjuna a sacred medicinal plant: phytochemical and pharmacological profile. Phytochem Rev 8:491–502
Jayaraj R, Anand T, Rao PL (2006) Activity and gene expression profile of certain antioxidant enzymes to microcystin-LR induced oxidative stress in mice. Toxicology 220:136–146
Kumar GP, Navya K, Ramya EM, Venkataramana M, Anand T, Anilakumar KR (2013) DNA damage protecting and free radical scavenging properties of Terminalia arjuna bark in PC-12 cells and plasmid DNA. Free Radic Antioxid 3:35–39
Lefebvre KA, Robertson A (2010) Domoic acid and human exposure risks: a review. Toxicon 56:218–230
Lelong A, Hégare H, Soudant P, Bates SS (2012) Pseudo-nitzschia (Bacillariophyceae) species, domoic acid and amnesic shellfish poisoning: revisiting previous paradigms. Phycologia 51:168–216
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Lu J, Wu DM, Zheng YL, Hu B, Cheng W, Zhang ZF, Li MQ (2013) Troxerutin counteracts domoic acid–induced memory deficits in mice by inhibiting CCAAT/enhancer binding protein β–mediated inflammatory response and oxidative stress. J Immunol 190:3466–3479
Ordonez AAL, Gomez JD, Vattuone MA (2006) Antioxidant activities of Sechium edule (Jacq.) Swartz extracts. Food Chem 97:452–458
Pulido OM (2008) Domoic acid toxicologic pathology: a review. Mar Drugs 6:180–219
Rahman K (2007) Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2:219–236
Rajendran P, Rengarajan T, Nandakumar N, Palaniswami R, Nishigaki Y, Nishigaki I (2014) Kaempferol, a potential cytostatic and cure for inflammatory disorders. Eur J Med Chem 86:103–112
Ramsdell JS, Gulland FM (2014) Domoic acid epileptic disease. Mar Drugs 12:1185–1207
Ruch RJ, Cheng SJ, Klaunig JE (1989) Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis 10:1003–1008
Samraj AK, Sohn D, Schulze-Osthoff K, Schmitz I (2007) Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization. Mol Biol Cell 18:84–93
Silvagni PA, Lowenstine LJ, Spraker T, Lipscomb TP, Gulland FMD (2005) Pathology of domoic acid toxicity in California sea lions (Zalophus californianus). Vet Pathol 42:184–191
Slinkard K, Singleton VL (1977) Total phenol analyses: automation and comparison with manual methods. Am J Enol Vitic 28:49e55
Sutherland RJ, Hoesing JM, Whishaw IQ (1990) Domoic acid, an environmental toxin, produces hippocampal damage and severe memory impairment. Neurosci Lett 120:221–223
Szende B, Kéri G, Szegedi Z, Benedeczky I, Csikos A, Örfi L, Gazit A (1995) Tyrphostin induces non-apoptotic programmed cell death in colon tumor cells. Cell Biol Int 19:903–912
Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74
Vranyac-Tramoundanas A, Harrison JC, Sawant PM, Kerr DS, Sammut IA (2011) Ischemic cardiomyopathy following seizure induction by domoic acid. Am J Pathol 179:141–154
Wattel A, Kamel S, Mentaverri R, Lorget F, Prouillet C, Petit JP, Brazier M (2003) Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol 65:35–42
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Authors are thankful to Director, DFRL, Mysore for providing constant guidance, encouragement and necessary facilities during this investigation.
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Ramya, E.M., Kumar, G.P., Anand, T. et al. Modulatory effects of Terminalia arjuna against domoic acid induced toxicity in Caco-2 cell line. Cytotechnology 69, 725–739 (2017). https://doi.org/10.1007/s10616-017-0080-9
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DOI: https://doi.org/10.1007/s10616-017-0080-9