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Protective effects of caffeic acid against hypothalamic neuropeptides alterations induced by malathion in rat

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Abstract

Exposure to pesticides is suspected to cause human health problems. Our study aimed to evaluate preventive effects of caffeic acid (3,4-dihydroxycinnamic acid) in the hypothalamus against malathion-induced neuropeptides gene expression alterations. Malathion at 100 mg/kg was administered intragastrically to rats alone or in combination with caffeic acid at 100 mg/kg during 4 weeks. A molecular expression of hypothalamic neuropeptides and plasmatic cholinesterase activity was investigated. Furthermore, we used in silico analysis, known as computational docking, to highlight the nature of acetylcholinesterase-malathion/caffeic acid interactions. Our findings showed differences in the responses and indicate that caffeic acid reversed malathion-induced decrease in corticotropin-releasing hormone mRNA but not brain-derived neurotrophic factor which presented an increased tendency. We suggest that caffeic acid can interact with acetylcholinesterase as the primary target of organophosphorus compounds. Results predict that caffeic acid can block partly the acetylcholinesterase gorge entrance via π-π stacking interaction with Tyr 124 and Trp 286 residues of the peripheral site leading to its stricture. Under this condition, we suggested that acetylcholine trafficking toward the catalytic site is ameliorated compared to malaoxon according to their sizes.

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References

  • Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A (2004) Pesticides and oxidative stress: a review. Med Sci Monit 10:RA141–RA147

    CAS  Google Scholar 

  • Abou-Donia MB (2003) Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health 58:484–497

    Article  CAS  Google Scholar 

  • Answar J, Spanevello RM, Thome G, Stefanello N, Schmatz R, Gutierres J, Vieira J, Baldisserotto J, Carvalho F, da Rosa MM, Rubin MA, Fiorenza A, Morsch VM, Schetinger MR (2012) Effects of caffeic acid on behavioral parameters and on the activity of acetylcholinesterase in different tissues from adult rats. Pharmacol, Biochem Behav 103:386–394

    Article  Google Scholar 

  • Burbach JP (2010) Neuropeptides from concept to online database www.neuropeptides.nl. Eur J Pharmacol 626:27–48

    Article  CAS  Google Scholar 

  • Chai L, Guo H, Li H, Wang S, Wang YL, Shi F, Hu LM, Liu Y, Adah D (2013) Scutellarin and caffeic acid ester fraction, active components of Dengzhanxixin injection, upregulate neurotrophins synthesis and release in hypoxia/reoxygenation rat astrocytes. J Ethnopharmacol 150:100–107

    Article  CAS  Google Scholar 

  • Chao X, He X, Yang Y, Zhou X, Jin M, Liu S, Cheng Z, Liu P, Wang Y, Yu J, Tan Y, Huang Y, Qin J, Rapposelli S, Pi R (2012) Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid hybrids as multi-targeted compounds against Alzheimer’s disease. Bioorg Med Chem Lett 22:6498–6502

    Article  CAS  Google Scholar 

  • Conforti F, Rigano D, Formisano C, Bruno M, Loizzo MR, Menichini F, Senatore F (2010) Metabolite profile and in vitro activities of Phagnalon saxatile (L.) Cass. relevant to treatment of Alzheimer's disease. J Enzyme Inhib Med Chem 25:97–104

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  Google Scholar 

  • Fortunato JJ, Feier G, Vitali AM, Petronilho FC, Dal-Pizzol F, Quevedo J (2006) Malathion-induced oxidative stress in rat brain regions. Neurochem Res 31:671–678

    Article  CAS  Google Scholar 

  • Fu W, Du G, Liu D, Ruan JL (2013) Neuroprotective effect of a caffeic acid derivative from Abacopteris penangiana. Pharm Biol 51:376–382

    Article  CAS  Google Scholar 

  • Hazarika A, Sarkar SN, Hajare S, Kataria M, Malik JK (2003) Influence of malathion pretreatment on the toxicity of anilofos in male rats: a biochemical interaction study. Toxicology 185:1–8

    Article  CAS  Google Scholar 

  • Hennig B, Ettinger AS, Jandacek RJ, Koo S, McClain C, Seifried H, Silverstone A, Watkins B, Suk WA (2007) Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases. Environ Health Perspect 115:493–495

    Article  CAS  Google Scholar 

  • Hennig B, Ormsbee L, McClain CJ, Watkins BA, Blumberg B, Bachas LG, Sanderson W, Thompson C, Suk WA (2012) Nutrition can modulate the toxicity of environmental pollutants: implications in risk assessment and human health. Environ Health Perspect 120:771–774

    Article  Google Scholar 

  • Hornberg A, Artursson E, Warme R, Pang YP, Ekstrom F (2010) Crystal structures of oxime-bound fenamiphos-acetylcholinesterases: reactivation involving flipping of the His447 ring to form a reactive Glu334-His447-oxime triad. Biochem Pharmacol 79:507–515

    Article  Google Scholar 

  • Jeanneteau FD, Lambert WM, Ismaili N, Bath KG, Lee FS, Garabedian MJ, Chao MV (2012) BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus. Proc Natl Acad Sci U S A 109:1305–1310

    Article  CAS  Google Scholar 

  • Jones G, Willett P, Glen RC, Leach AR, Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267:727–748

    Article  CAS  Google Scholar 

  • Khan KA, Kumar N, Nayak PG, Nampoothiri M, Shenoy RR, Krishnadas N, Rao CM, Mudgal J (2013) Impact of caffeic acid on aluminium chloride-induced dementia in rats. J Pharm Pharmacol 65:1745–1752

    Article  CAS  Google Scholar 

  • Ludwig M (2011) Are neuropeptides brain hormones? J Neuroendocrinol 23:381–382

    Article  CAS  Google Scholar 

  • Mostafalou S, Abdollahi M (2013) Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol 268:157–177

    Article  CAS  Google Scholar 

  • Noble EE, Billington CJ, Kotz CM, Wang C (2011) The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol 300:R1053–R1069

    Article  CAS  Google Scholar 

  • Oboh G, Agunloye OM, Akinyemi AJ, Ademiluyi AO, Adefegha SA (2013) Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer’s disease and some pro-oxidant induced oxidative stress in rats’ brain-in vitro. Neurochem Res 38:413–419

    Article  CAS  Google Scholar 

  • Papadimitriou A, Priftis KN (2009) Regulation of the hypothalamic-pituitary-adrenal axis. Neuroimmunomodulation 16:265–271

    Article  CAS  Google Scholar 

  • Rehman MU, Sultana S (2011) Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats. Mol Cell Biochem 357:115–124

  • Rezg R, Mornagui B, El-Arbi M, Kamoun A, El-Fazaa S, Gharbi N (2006) Effect of subchronic exposure to malathion on glycogen phosphorylase and hexokinase activities in rat liver using native PAGE. Toxicology 223:9–14

    Article  CAS  Google Scholar 

  • Rezg R, Mornagui B, Kamoun A, El-Fazaa S, Gharbi N (2007) Effect of subchronic exposure to malathion on metabolic parameters in the rat. C R Biol 330:143–147

    Article  CAS  Google Scholar 

  • Rezg R, Benahmed M, Mornagui B, El-Fazaa S, Gharbi N (2008a): Effect of subchronic exposure to an organophosphorus compound on corticotropin releasing factor mRNA expression in rat hypothalamus. Toxicology Letters 180, Supplement, S174

  • Rezg R, Mornagui B, El-Fazaa S, Gharbi N (2008b) Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity. Toxicology 250:27–31

    Article  CAS  Google Scholar 

  • Rezg R, Mornagui B, Benahmed M, Chouchane SG, Belhajhmida N, Abdeladhim M, Kamoun A, El-fazaa S, Gharbi N (2010a) Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats. Food Chem Toxicol 48:1473–1477

    Article  CAS  Google Scholar 

  • Rezg R, Mornagui B, El-Fazaa S, Gharbi N (2010b) Organophosphorus pesticides as food chain contaminants and type 2 diabetes: a review. Trends Food Sci Technol 21:345–357

    Article  CAS  Google Scholar 

  • Sondheimer E (1958) On the distribution of caffeic acid and the chlorogenic acid isomers in plants. Arch Biochem Biophys 74:131–138

    Article  CAS  Google Scholar 

  • Tait S, Ricceri L, Venerosi A, Maranghi F, Mantovani A, Calamandrei G (2009) Long-term effects on hypothalamic neuropeptides after developmental exposure to chlorpyrifos in mice. Environ Health Perspect 117:112–116

    Article  CAS  Google Scholar 

  • Takeda H, Tsuji M, Yamada T, Masuya J, Matsushita K, Tahara M, Iimori M, Matsumiya T (2006) Caffeic acid attenuates the decrease in cortical BDNF mRNA expression induced by exposure to forced swimming stress in mice. Eur J Pharmacol 534:115–121

    Article  CAS  Google Scholar 

  • Touaibia M, Jean-Francois J, Doiron J (2011) Caffeic acid, a versatile pharmacophore: an overview. Mini Rev Med Chem 11:695–713

    Article  CAS  Google Scholar 

  • Tsagarakis S, Grossman A (1994) Corticotropin-releasing hormone: interactions with the immune system. Neuroimmunomodulation 1:329–334

    Article  CAS  Google Scholar 

  • Tsai SJ, Chao CY, Yin MC (2011) Preventive and therapeutic effects of caffeic acid against inflammatory injury in striatum of MPTP-treated mice. Eur J Pharmacol 670:441–447

    Article  CAS  Google Scholar 

  • Tsigos C, Chrousos GP (1994) Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation in psychiatric and autoimmune disorders. Endocrinol Metab Clin North Am 23:451–466

    CAS  Google Scholar 

  • Uluitu M, Boca A, Petec G, Chis R, Catrinescu G (1981) The influence of malathion on the brain serotonin and reproductive function in rats. Physiologie 18:167–174

    CAS  Google Scholar 

  • Venerosi A, Ricceri L, Tait S, Calamandrei G (2012) Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos. Neurotoxicology 33:1420–1426

    Article  CAS  Google Scholar 

  • Viswanath G, Chatterjee S, Dabral S, Nanguneri SR, Divya G, Roy P (2010) Anti-androgenic endocrine disrupting activities of chlorpyrifos and piperophos. J Steroid Biochem Mol Biol 120:22–29

    Article  CAS  Google Scholar 

  • Yang JQ, Zhou QX, Liu BZ, He BC (2008) Protection of mouse brain from aluminum-induced damage by caffeic acid. CNS Neurosci Ther 14:10–16

    Article  CAS  Google Scholar 

  • Zhou Y, Fang SH, Ye YL, Chu LS, Zhang WP, Wang ML, Wei EQ (2006) Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats. Acta Pharmacol Sin 27:1103–1110

    Article  CAS  Google Scholar 

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Funding Acknowledgement

This work was supported by the Tunisian Ministry of Higher Education and Scientific Research. We are grateful to AUF (Agence Universitaire de la Francophonie) for awarding postdoctoral grants.

Guidelines for Ethical Publications

The authors declare that this manuscript was consistent with the guidelines and principles of the American College of Toxicology Statement on the Use of Animals in Toxicology.

Conflict of interests

The authors declared no potential conflicts of interest.

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Authors and Affiliations

  1. Laboratoire de Physiologie des Agressions, Département de Biologie, Faculté des Sciences de Tunis, Université El Manar, Tunis, Tunisie

    Raja Rezg, Bessem Mornagui, Saloua El-Fazaa & Najoua Gharbi

  2. Centre d’Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Universite de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032, Caen Cedex, France

    Jana Sopkova-de Oliveira Santos, Fabienne Dulin & Ronan Bureau

  3. Département des Sciences de la Vie, Faculté des Sciences de Gabès, Université de Gabès, Zrig Gabès, Tunisie

    Bessem Mornagui & Noomen Ben El-haj

  4. Département de Biotechnologie, Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisie

    Raja Rezg

  5. Département des Sciences de la Vie, Faculté des Sciences de Gabès, Cité Erriadh, 6072, Zrig Gabès, Tunisie

    Bessem Mornagui

Authors
  1. Raja Rezg
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  2. Bessem Mornagui
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  8. Najoua Gharbi
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Corresponding author

Correspondence to Bessem Mornagui.

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Responsible editor: Philippe Garrigues

Raja Rezg and Bessem Mornagui have equally contributed to this work.

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Rezg, R., Mornagui, B., Santos, J.Sd.O. et al. Protective effects of caffeic acid against hypothalamic neuropeptides alterations induced by malathion in rat. Environ Sci Pollut Res 22, 6198–6207 (2015). https://doi.org/10.1007/s11356-014-3824-5

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  • DOI: https://doi.org/10.1007/s11356-014-3824-5

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