Modulation of paraoxonase activity (PON)-1 by xanthone in sub chronic exposure of orgnophosphate: Antioxidant in dichorvos intoxicity

  • Titin Andri WihastutiEmail author
  • Djanggan Sargowo
  • Teuku Heriansyah
  • Grace Rahmawati
  • Yuni Hendrati Sulfia
Research Article


This research aims to find out the levels of xanthone in mangosteen pericarp extract (MPE) and to prove the ability of xanthone in modulating the activity of paraoxonase-1 (PON-1), reduce oxidized-low density lipoprotein (ox-LDL) and increase the levels of acetylcholinesterase (AChE) serum in animal model with organophosphat subchronic and subcutaneous exposure. This research is a true experimental laboratory with in vivo approach to post-test with control group, using 25 animal models of Wistar strain of Rattus novergicus, were exposed to dichlorvos as organophosphates (2 mg/kgBW/day) for 21 days. Those animal models are divided into no exposure group, organophosphate exposure group, and organophosphate exposure plus administration of xanthone groups. The parameters (levels of PON-1, ox-LDL and AChE measured by ELISA Test. The results showed that administration of xanthone significantly increased the levels of AChE, decreased levels of ox-LDL and PON-1.


PON-1 ox-LDL AChE Mangosteen pericarp extract Xanthone Organophosphat 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Karami-Mohajeri, S. & Abdollahi, M. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum. Exp. Toxicol. 30, 1119–1140 2011.PubMedCrossRefGoogle Scholar
  2. 2.
    Bolognesi, C. Genotoxicity of pesticides: A review of human biomonitoring studies. Mutat. Res. - Rev. Mutat. Res. 543, 251–272 2003.CrossRefGoogle Scholar
  3. 3.
    Ha, J. C. & Richman, D. P. Myasthenia gravis and related disorders: Pathology and molecular pathogenesis. Biochim. Biophys. Acta 1852, 651–657 2015.PubMedCrossRefGoogle Scholar
  4. 4.
    De Sousa Rios, M. A. & Mazzetto, S. E. Effect of organophosphate antioxidant on the thermo-oxidative degradation of a mineral oil. J. Therm. Anal. Calorim. 111, 553–559 2012.CrossRefGoogle Scholar
  5. 5.
    Leibson, T. & Lifshitz, M. Organophosphate and carbamate poisoning: Review of the current literature and summary of clinical and laboratory experience in Southern Israel. Isr. Med. Assoc. J. 10, 767–770 2008.PubMedGoogle Scholar
  6. 6.
    Lukaszewicz-Hussain, A. Role of oxidative stress in organophosphate insecticide toxicity - Short review. Pestic. Biochem. Physiol. 98, 145–150 2010.CrossRefGoogle Scholar
  7. 7.
    Sarbini, D., Sargowo, D. & Rohman, M. S. The Effect of Red Rosella Tea (Hibiscus sabdariffa Linn) on the Inhibition of NF-?B Activation, TNF-a and ICAM-1- Protein Expressions Following Treatment with Ox-LDL in HUVECs. J. Kardiol. Ind. 28, 133–141 2007.Google Scholar
  8. 8.
    Klein, G. M., Nelson, L. S. & Farmer, B. M. Mechanisms of Action of Organophosphorus Pesticides and Nerve Agents. Postgrad. Inst. Med. 4-7 (2009).Google Scholar
  9. 9.
    El-Demerdash, F. M. Lipid peroxidation, oxidative stress and acetylcholinesterase in rat brain exposed to organophosphate and pyrethroid insecticides. Food Chem. Toxicol. 49, 1346–1352 2011.PubMedCrossRefGoogle Scholar
  10. 10.
    Costa, L. G., Vitalone, A., Cole, T. B. & Furlong, C. E. Modulation of paraoxonase (PON1) activity. Biochem. Pharmacol. 69, 541–550 2005.PubMedCrossRefGoogle Scholar
  11. 11.
    Costa, L. G., Cole, T. B., Jarvik, G. P. & Furlong, C. E. Functional genomic of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annu. Rev. Med. 54, 371–392 2003.PubMedCrossRefGoogle Scholar
  12. 12.
    Jung, H.-A., Su, B.-N., Keller, W. J., Mehta, R. G. & Kinghorn, A. D. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J. Agric. Food Chem. 54, 2077–2082 2006.PubMedCrossRefGoogle Scholar
  13. 13.
    Toxicity and Exposure Assessment for Children’s Health U.S. EPA. Dichlorvos. J. Cross. Cult. Gerontol. 1, 113–115 2007.Google Scholar
  14. 14.
    Yadav, P. et al. Protective efficacy of 2-PAMCl, atropine and curcumin against dichlorvos induced toxicity in rats. Interdiscip. Toxicol. 5, 1–8 2012.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Costa, Lucio G. & Furlong, C. E. Paraoxonase (PON1) In Health and Disease: Basic and Clinical Aspects. Springer Sci. 15, 165–186 2007.Google Scholar
  16. 16.
    Harel, M. et al. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat. Struct. Mol. Biol. 11, 412–419 2004.PubMedCrossRefGoogle Scholar
  17. 17.
    Harel, M. et al. 3-D structure of serum paraoxonase 1 sheds light on its activity, stability, solubility and crystallizability. Arh. Hig. Rada Toksikol. 58, 347–353 2007.PubMedCrossRefGoogle Scholar
  18. 18.
    Rosenblat, M. et al. Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress. Arterioscler. Thromb. Vasc. Biol. 23, 468–474 2003.CrossRefGoogle Scholar
  19. 19.
    Jiang, D.-J., Dai, Z. & Li, Y.-J. Pharmacological effects of xanthones as cardiovascular protective agents. Car-diovasc. Drug Rev. 22, 91–102 2004.CrossRefGoogle Scholar
  20. 20.
    Gutierrez-Orozco, F. & Failla, M. L. Biological activities and bioavailability of mangosteen xanthones: A critical review of the current evidence. Nutrients 5, 3163–3183 2013.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Kondo, M., Zhang, L., Ji, H., Kou, Y. & Ou, B. Bioavailability and antioxidant effects of a xanthone-rich mangosteen (Garcinia mangostana) product in humans. J. Agric. Food Chem. 57, 8788–8792 2009.PubMedCrossRefGoogle Scholar
  22. 22.
    Shenouda, J., Green, P. & Sultatos, L. An Evaluation of the Inhibition of Human Butyrylcholinesterase and Acetylcholinesterase by the Organophosphate Chlorpyrifos Oxon. Changes 29, 997–1003 2012.Google Scholar

Copyright information

© Korean Society of Environmental Risk Assessment and Health Science and Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Titin Andri Wihastuti
    • 1
    Email author
  • Djanggan Sargowo
    • 2
  • Teuku Heriansyah
    • 3
  • Grace Rahmawati
    • 4
  • Yuni Hendrati Sulfia
    • 4
  1. 1.Department of Biomedical, Faculty of MedicineBrawijaya UniversityMalangIndonesia
  2. 2.Department of Cardiology, Faculty of MedicineBrawijaya UniversityMalangIndonesia
  3. 3.Department of Cardiology, Faculty of MedicineSyiah Kuala UniversityAcehIndonesia
  4. 4.Brawijaya UniversityMalangIndonesia

Personalised recommendations