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Morus alba leaf extract mediates neuroprotection against glyphosate-induced toxicity and biochemical alterations in the brain

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Abstract

Recent studies demonstrate that glyphosate exposure is associated with oxidative stress and some neurological disorders such as Parkinson’s pathology. Therefore, phytochemicals, in particular phenolic compounds, have attracted increasing attention as potential agents for neuroprotection. In the present study, we investigate the impact of glyphosate on the rat brain following i.p. injection and the possible molecular target of neuroprotective activity of the phenolic fraction from Morus alba leaf extract (MALE) and its ability to reduce oxidative damage in the brain. Wistar rats from 180 to 240 g were i.p. treated with a single dose of glyphosate (100 mg kg−1 b.w.) or MALE (100 μg mL−1 kg−1 b.w.) for 2 weeks. Brain homogenates were used to evaluate neurotoxicity induced by the pesticide. For this, biochemical parameters were measured. Data shows that MALE regulated oxidative stress and counteracted glyphosate-induced deleterious effects and oxidative damage in the brain, as it abrogated LDH, protein carbonyls, and malonyldialdehyde. MALE also appears to be able to scavenge H2O2 levels, maintain iron and Ca2+ homeostasis, and increase SOD activity. Thus, in vivo results showed that mulberry leaf extract is a potent protector against glyphosate-induced toxicity, and its protective effect could result from synergism or antagonism between the various bioactive phenolic compounds in the acetonic fraction from M. alba leaf extract.

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Abbreviations

MALE:

Morus alba leaf extract

b.w:

Body weight

i.p:

Intra-peritonial

SOD:

Superoxide dismutase

LDH:

Lactate dehydrogenase

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate

PD:

Parkinson’s disease

POD:

Peroxidase

MDA:

Malondialdehyde

References

  • Abed El-Hamid SR, Refaie AA (2009) Ameliorative effect of Silybum marianum extract againist avermectin induced toxicity in adult male rats. JASMR 4:25–31

    Google Scholar 

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

    Article  CAS  Google Scholar 

  • Astiz M, De Alaniz MJT, Marra CA (2009a) Antioxidant defense system in rats simultaneously intoxicated with agrochemicals. Environ Toxicol Pharmacol 28:465–473

    Article  CAS  Google Scholar 

  • Astiz M, De Alaniz MJT, Marra CA (2009b) Effect of pesticides on cell survival in liver and brain rat tissues. Ecotoxicol Environ Saf 72:2025–2032

    Article  CAS  Google Scholar 

  • Astiz M, De Alaniz MJ, Marra CA (2012) The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain. Neurochem Int 61:1231–1241

    Article  CAS  Google Scholar 

  • Barbosa ER, Leiros da Costa MD, Bacheschi LA, Scaff M, Leite CC (2001) Parkinsonism after glycine-derivate exposure. Mov Disord 16:565–568

    Article  CAS  Google Scholar 

  • Barbouti A, Amorgianiotis C, Kolettas E, Kanavaros P, Galaris D (2007) Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Rad Biol Med 43:1377–1387

    Article  CAS  Google Scholar 

  • Battaglin WA, Meyer MT, Kuivila KM, Dietze JE (2014) Glyphosate and its degradation product AMPA occur frequently and widely in U.S. soils, surface water, groundwater, and precipitation. J Am Water Resour Assoc 50:275–290

    Article  CAS  Google Scholar 

  • Beuret CJ, Zirulnik F, Gimenez MS (2005) Effect of the herbicide glyphosate on liver lipoperoxidation in pregnant rats and their fetuses. Reprod Toxicol 19:501–504

    Article  CAS  Google Scholar 

  • Butt MS, Nazir A, Sultan MT, Schroeon K (2008) Morus alba L. nature’s functional tonic. Trends Food Sci Technol 19:505–e512

    Article  CAS  Google Scholar 

  • Castellani R, Smith MA, Richey GL, Perry G (1996) Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease. Brain Res 737:195–200

    Article  CAS  Google Scholar 

  • Castro J, Bittner CX, Humeres A, Montecinos VP, Vera JC, Barros LF (2004) Acytosolic source of calcium unveiled by hydrogen peroxide with relevance for epithelial cell death. Cell Death Differ 11:468–478

    Article  CAS  Google Scholar 

  • Cattani D, de Liz Oliveira Cavalli VL, Heinz Rieg CE, Domingues JT, Dal-Cim T, Tasca CI, Mena Barreto Silva FR, Zamoner A (2014) Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: involvement of glutamate excitotoxicity. Toxicology 320:34–45

  • Cavuşoğlu K, Yapar K, Oruç E, Yalçın E (2011) Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice. J Med Food 14(10):1263–1272

    Article  Google Scholar 

  • Chorfa A, Bétemps D, Morignat E, Lazizzera C, Hogeveen K, Andrieu T, Baron T (2013) Specific pesticide-dependent increases in _-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines. Toxicol Sci 133:289–297

    Article  CAS  Google Scholar 

  • Daruich J, Zirulnik F, Gimenez MS (2001) Effect of the herbicide glyphosate on enzymatic activity in pregnant rats and their fetuses. Environ Res Sect A 85:226–231

    Article  CAS  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinsons disease: mechanisms and models. Neuron 39:889–909

    Article  CAS  Google Scholar 

  • De Liz Oliveira Cavalli LV, Cattani D, Heinz Rieg CE, Pierozan P, Zanatta L, Benedetti Parisotto E et al (2013) Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells. Free Radic Biol Med 65:335–346

    Article  Google Scholar 

  • Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    Article  CAS  Google Scholar 

  • Dutta U, Cohenford MA, Guha M, Dain JA (2007) Non-enzymatic interactions of glyoxylate with lysine, arginine, and glucosamine: a study of advanced non-enzymatic glycation like compounds. Bioorg Chem 35:11–24

    Article  CAS  Google Scholar 

  • El-Shenawy NS (2009) Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate. Environ Toxicol Pharmacol 28:379–385

    Article  CAS  Google Scholar 

  • Fattouch S, CaboniP CV, Tuberoso C, Angioni A, Dessi S, Marzouki MN, Cabras P (2008) Comparative analysis of polyphenolic profiles and antioxidant and antimicrobial activities of Tunisian pome fruit pulp and peel aqueous acetone extracts. J Agric Food Chem 56:1084–1090

    Article  CAS  Google Scholar 

  • Gui YX, Fan XN, Wang HM, Wang G, Chen SD (2012) Glyphosate induced cell death through apoptotic and autophagic mechanisms. Neurotoxicol Teratol 34:344–349

    Article  CAS  Google Scholar 

  • Joseph L, Ryan J Mailloux, and Vasu D (2008) Mitochondrial lactate dehydrogenase is involved in oxidative-energy metabolism in human astrocytoma cells (CCF-STTG1). PLoS ONE 1550

  • Kaneta H, Fujii J, Suzuki K, Kasai H, Kawamore R, Kamadaa T (1994) DNA cleavage induced by glycation of Cu, Zn-superoxide dismutase. Biochem J 304:219–225

    Article  Google Scholar 

  • Kang TH, Oh H, Jung SM, Ryu JH, Park MW, Park YK, Kim SY (2006) Enhancement of neuroprotection of mulberry leaves (Morus alba L.) prepared by the anaerobic treatment against ischemic damage. Biol Pharm Bull 29(2):270–274

    Article  CAS  Google Scholar 

  • Khan SM (2005) Protective effect of black tea extract on the levels of lipid peroxidation and antioxidant enzymes in liver of mice with pesticide-induced liver injury. Cell Biochem Funct 24:327–332

    Article  Google Scholar 

  • Krüger M, Schrödl W, Pedersen I, Shehata AA (2014) Detection of glyphosate in malformed piglets. J Environ Anal Toxicol 4:5

    Article  Google Scholar 

  • Leardi A, Caraglia M, Selleri C et al (1998) Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells. Brit J Haematol 102:746–752

    Article  CAS  Google Scholar 

  • Lee CY, Sim SM, Cheng HM (2007) Systemic absorption of antioxidants from mulberry (Morus alba L) leaf extracts using an in situ rat intestinal preparation. Nutr Res 27:492–497

    Article  CAS  Google Scholar 

  • Lushchak OV, Kubrak OI, Storey JM, Storey KB, Lushchak VI (2009) Low toxic herbicide Roundup induces mild oxidative stress in goldfish tissues. Chemosphere 76:932–937

    Article  CAS  Google Scholar 

  • Merhi M, Demur C, Racaud-Sultan C, Bertrand J, Canlet C, Estrada F, Gamet-Payrastre L (2010) Gender-linked haematopoietic and metabolic disturbances induced by a pesticide mixture administered at low dose to mice. Toxicology 267:80–90

    Article  CAS  Google Scholar 

  • Misra HP, Fridovich I (1972) The role of superoxide anion in autoxidation of epinephrine and a simple assay for SOD. J Biol Chem 247:3170–3175

    CAS  Google Scholar 

  • Mokni M, Hamlaoui-Guesmi S, Amri M, Marzouki L, Limam F, Aouani E (2012) Grape seed and skin extract protects against acute chemotherapy toxicity induced by doxorubicin in rat heart. Cardiovasc Toxicol

  • Negga R, Stuart JA, Machen ML, Salva J, Lizek AJ, Richardson SJ (2012) Exposure to glyphosate- and/or Mn/Zn-ethylene-bisdithiocarbamate-containing pesticides leads to degeneration of γ-aminobutyric acid and dopamine neurons in Caenorhabditis elegans. Neurotox Res 21:281–290

    Article  CAS  Google Scholar 

  • Niidome T, Takahashi K, Goto Y, Goh SM, Tanaka N, Kamei K (2007) Mulberry leaf extract prevents amyloid beta-peptide fibril formation and neurotoxicity. Neuro report 18:813–816

    Google Scholar 

  • Ohnishi ST, Barr JK (1978) A simple method of quantitating protein using the biuret and phenol reagent. Anal Biochem 86:193–200

    Article  CAS  Google Scholar 

  • Olorunsogo OO (1990) Modification of the transport of protons and Ca2+ ions across mitochondrial coupling membrane by N-(phosphonomethyl) glycine. Toxicology 61:205–209

  • Peng CH, Liu LK, Chuang CM, Chyau CC, Huang CN, Wang CJ (2011) Mulberry water extracts possess an anti-obesity effect and ability to inhibit hepatic lipogenesis and promote lipolysis. J Agric Food Chem 59(6):2663–2671

  • Rizvi SI, Maurya PK (2007) Markers of oxidative stress in erythrocytes during aging in humans. Ann N Y Acad Sci 1100:373–382

    Article  CAS  Google Scholar 

  • Shehata AA, Schrödl W, Schledorn P, Krüger M (2014) Distribution of glyphosate in chicken organs and its reduction by humic acid supplementation. J Poult Sci 51:333

    Article  CAS  Google Scholar 

  • Stern J, Lewis WH (1957) The colorimetric estimation of calcium in serum with ocresolphthalein complexone. Clin Chim Acta 2:576–580

    Article  CAS  Google Scholar 

  • Tong HK, Hye RO, Sun MJ, Jong HR, Mee WP, Yong KP, Sun YK (2006) Enhancement of neuroprotection of mulberry leaves (Morus alba L.) prepared by the anaerobic treatment against ischemic damage. Biol Pharm Bull 29:270–274

    Article  Google Scholar 

  • Yamakura F, Kawasaki H (2009) Post-translational modifications of superoxide dismutase. Biochim Biophys Acta 1804:318–325

    Article  Google Scholar 

  • Yoshioka T, Homma T, Meyrick B (1994) Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells. Kidney Int 46:405–413

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Research Unit 00-UR-08-01. We gratefully acknowledge the financial support of the Tunisian Ministry of High Education, Scientific Research and Technology.

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Correspondence to Olfa Rebai.

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Responsible editor: Philippe Garrigues

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Rebai, O., Belkhir, M., Boujelben, A. et al. Morus alba leaf extract mediates neuroprotection against glyphosate-induced toxicity and biochemical alterations in the brain. Environ Sci Pollut Res 24, 9605–9613 (2017). https://doi.org/10.1007/s11356-017-8584-6

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  • DOI: https://doi.org/10.1007/s11356-017-8584-6

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