Skip to main content

Advertisement

SpringerLink
Log in

Diazinon, an organophosphate pesticide, induces oxidative stress and genotoxicity in cells deriving from large intestine

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Diazinon (DZ) (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl]phosphorothioate) is an organophosphate pesticide which is extensively used to control household insects and fruit and vegetable crops. The exposure to this pesticide has been linked to the development of the serious problem in several experimental animals. The contamination of food by DZ may increase its danger to humans. The aim of this study was to investigate the toxic effect of DZ on intestine using an in vitro model (HCT116). Therefore, we evaluated the cell viability, elucidated the generation of free radicals, measured the mitochondrial membrane potential, and valued DNA fragmentation. Our results showed that DZ is cytotoxic to HCT116. It causes oxidative damage through the generation of free radicals and induces lipid peroxidation and DNA fragmentation. We also demonstrated that such effects can be responsible for DZ-induced apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Akturk O, Demirin H, Sutcu R, Yilmaz N, Koylu H, Altuntas I (2006) The effects of diazinon on lipid peroxidation and antioxidant enzymes in rat heart and ameliorating role of vitamin E and vitamin C. Cell Biol Toxicol 22(6):455–461

    Article  CAS  Google Scholar 

  • Baily HC, Deanovic L, Reyes E, Kimball T, Larson K, Conner V, Hinton DE (2000) Diazinon and chlorpyrifos in urban waterways in northern California, USA. Environ Toxicol Chem 19:82–87

    Article  Google Scholar 

  • Ben Salem I, Boussabbeh M, Bacha H, Abid S (2015) Dichlorvos-induced toxicity in HCT116 cells: Involvement of oxidative stress and apoptosis. Pestic Biochem Physiol 119:62–66

    Article  CAS  Google Scholar 

  • Brondz I (2015) High-performance liquid chromatograph (HPLC) equipped with a neurophysiological detector (NPD) as a tool for studying olfactory system intoxication by the organophosphate (OP) pesticide diazinon and the influence of OP pesticides on reproduction. Int J Anal Mass Spectrom Chromatogr 3:14–24

    Article  Google Scholar 

  • Cakici O, Akat E (2013) Effects of oral exposure to diazinon on mice liver and kidney tissues: biometric analyses of histopathologic changes. Anal Quant Cytol Histol 35:7–16

    Google Scholar 

  • Cao J, Liu Y, Jia L, Zhou HM, Kong Y, Yang G, Jiang LP, Li QJ, Zhong LF (2007) Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. Free Radic Biol Med 43:968–975

    Article  CAS  Google Scholar 

  • Castilho RF, Meinicke AR, Almeida AM, Hermes-Lima M, Vercesi AE (1994) Oxidative damage of mitochondria induced by Fe(II)citrate is potentiated by Ca2+ and includes lipid peroxidation and alterations in membrane proteins. Arch Biochem Biophys 308:158–164

    Article  CAS  Google Scholar 

  • Castilho RF, Meinicke AR, Vercesi AE, And Hermes-Lima M (1999) The role of Fe(III) in Fe(II)-citrate mediated peroxidation of mitochondrial membrane lipids. Mol Cell Biochem 196:163–168

    Article  CAS  Google Scholar 

  • Cathcart R, Schwiers E, Ames BN (1983) Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. Anal Biochem 134:111–116

    Article  CAS  Google Scholar 

  • Chae HD, Kim BM, Yun UJ, Shin DY (2008) Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage. Oncogene 27:4115–4121

    Article  CAS  Google Scholar 

  • Chen T, Wong YS (2009) Selenocystine induces caspase-independent apoptosis in MCF-7 human breast carcinoma cells with involvement of p53 phosphorylation and reactive oxygen species generation. Int J Biochem Cell Biol 41:666–676

    Article  CAS  Google Scholar 

  • Chengzhi L (2009) The effects of cadmium on heme oxygenase-1 in HCT116 human colon epithelial cells with or without iron deficiency. Thesis

  • Clayton AC, Pellizzari ED, Whitmore RW, Quackenboss JJ, Adgate J, Sefton K (2003) Distributions, associations and partial aggregate exposure of pesticides and polynuclear aromatic hydrocarbons in the Minnesota Children’s Pesticide Exposure Study (MNCPES). J Expo Anal Environ Epidemiol 13:100–111

    Article  CAS  Google Scholar 

  • Collins AR, Dusinska M, Gedik CM, Stetina R (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104:465–469

    Article  CAS  Google Scholar 

  • Čolović MB, Vasića VM, Avramović NS, Gajić MM, Djurić DM, Krstić DZ (2015) In vitro evaluation of neurotoxicity potential and oxidative stress responses of diazinon and its degradation products in rat brain synaptosomes. Toxicol Lett 23(1):29–37

    Google Scholar 

  • Debbasch C, Brignole F, Pisella PJ, Warnet JM, Rat P, Baudouin C (2001) Quaternary ammoniums and other preservatives’ contribution in oxidative stress and apoptosis on Chang conjunctival cells. Invest Ophthalmol Vis Sci 42:642–652

    CAS  Google Scholar 

  • Drufovka K, Trebse P, Stopar D (2008) Microorganisms trigger chemical degradation of diazinon. Int Biodeterior Biodegrad 62(3):293e296

    Article  CAS  Google Scholar 

  • El-Khatib M, Geara F, Haddadin MJ, Gali-Muhtasib H (2010) Cell death by the quinoxaline dioxide DCQ in human colon cancer cells is enhanced under hypoxia and is independent of p53 and p21. Radiat Oncol 5:107

    Article  CAS  Google Scholar 

  • EU Pesticides database (2013) Pesticide EU-MRLs. Regulation EC No. 396/2005. Retrieved from http://ec.europa.eu/sanco_pesticides. Accessed 17 Apr 2013

  • Fulton MH, Key PB (2001) Acetylcholinesterase inhibition in estuarine fish and invertebrates as an indicator of organophosphorus insecticide exposure and effects. Environ Toxicol Chem 20:37–45

    Article  CAS  Google Scholar 

  • Gokcimen A, Gulle K, Demirin H, Bayram D, Kocak A, Altuntas I (2007) Effects of diazinon at different doses on rat liver and pancreas tissues. Pestic Biochem Physiol 87:103–108

    Article  CAS  Google Scholar 

  • Gomes A, Fernandes E, Lima JL (2005) Fluorescence probes used for detection of reactive oxygen species. J Biochem Biophys Methods 65:45–80

    Article  CAS  Google Scholar 

  • Halim Mossa AT, Heikal TM, Mostafa S, Mohafrash SMM (2014) Lipid peroxidation and oxidative stress in rat erythrocytes induced by aspirin and diazinon: the protective role of selenium. Asian Pac J Trop Biomed 4(2):603–609

    Article  Google Scholar 

  • Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H (2010) Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal. Food Chem Toxicol 48(10):2803–2808

    Article  CAS  Google Scholar 

  • Hermes-Lima M, Castilho RF, Meinicke AR, Vercesi AE (1995) Characteristics of Fe(II)ATP complex-induced damage to the rat liver mitochondria. Mol Cell Biochem 145:53–60

    Article  CAS  Google Scholar 

  • Kalender S, Ogutcu A, Uzunhisarcikli M, Açikgoz F, Durak D, Ulusoy Y, Kalender Y (2005) Diazinon-induced hepatotoxicity and protective effect of vitamin E on some biochemical indices and ultrastructural changes. Toxicology 211:197–206

    Article  CAS  Google Scholar 

  • Kamanyire R, Karalliedde L (2004) Organophosphate toxicity and occupational exposure. Occup Med 54:69–75

    Article  CAS  Google Scholar 

  • Kowaltowski AJ, Castilho RF, Grijalba MT, Bechara EJH, Vercesi AE (1996) Effect of inorganic phosphate concentration on the nature of inner mitochondrial membrane alterations mediated by Ca2+ ions. A proposed model for phosphate-stimulated lipid peroxidation. J Biol Chem 271:2929–2934

    Article  CAS  Google Scholar 

  • Kowaltowski AJ, Castilho RF, Vercesi AE (2001) Mitochondrial permeability transition and oxidative stress. FEBS Lett 495:12–15

    Article  CAS  Google Scholar 

  • Le Bel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2-,7-dichlorofluorescein as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231

    Article  Google Scholar 

  • Lecoeur S, Videmann B, Mazallon M (2006) Effect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein. Toxicol Lett 161:200–209

    Article  CAS  Google Scholar 

  • Malley MO (1997) Clinical evaluation of pesticide exposure and poisonings. Lancet 349:1161–1166

    Article  Google Scholar 

  • Maroni M, Catenacci G, Galli D, Cavallo D, Ravazzani G (1990) Biological monitoring of human exposure to acephate. Arch Environ Contam Toxicol 19(5):782–788

    Article  CAS  Google Scholar 

  • McCauley LA, Michaels S, Rothlein J, Muniz J, Lasarev M, Ebbert C (2003) Pesticide exposure and self-reported home hygiene: practices in agricultural families. AAOHN J 51:113–119

    Google Scholar 

  • Mosman T (1983) Rapid colorimetric assay for cellular growth and survival. Application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  Google Scholar 

  • Ogutcu A, Uzunhisarcikli M, Kalender S, Durak D, Bayrakdar F, Kalender Y (2006) The effects of organophosphate insecticide diazinon on malondialdehyde levels and myocardial cells in rat heart tissue and protective role of vitamin E. Pestic Biochem Physiol 86(2):93–98

    Article  CAS  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxide in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  Google Scholar 

  • Oksay T, Nazıroğlu M, Ergün O, Doğan S, Özatik O, Armağan A, Özorak A, Çelik Ö (2013) N-Acetyl cysteine attenuates diazinon exposure-induced oxidative stress in rat testis. Andrologia 45(3):171–177

    Article  CAS  Google Scholar 

  • Oruc EO, Usta D (2007) Evaluation of oxidative stress responses and neurotoxicity potential of diazinon in different tissues of Cyprinus carpio. Environ Toxicol Pharmacol 23:48–55

    Article  CAS  Google Scholar 

  • Pirsaheb M, Fattahi N, Pourhaghighat S, Shamsipur M, Sharafi K (2015) Simultaneous determination of imidacloprid and diazinon in apple and pear samples using sonication and dispersive liquid-liquid microextraction. Food Sci Technol 60:825e831

    Google Scholar 

  • Razavi BM, Hosseinzadeh H, Movassaghi AR, Imenshahidi M, Abnous K (2013) Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem Biol Interact 203:547–555

    Article  CAS  Google Scholar 

  • Razavi BM, Hosseinzadeh H, Imenshahidi M, Malekian M, Ramezani M, Abnous K (2014) Evaluation of protein ubiquitylation in heart tissue of rats exposed to diazinon (an organophosphate insecticide) and crocin (an active saffron ingredient): role of HIF-1α. Drug Res. doi:10.1055/s-0034-1384533

    Google Scholar 

  • Roegge CS, Timofeeva OA, Seidler FJ, Slotkin TA, Levin ED (2008) Developmental diazinon neurotoxicity in rats: later effects on emotional response. Brain Res Bull 75:166–172

    Article  CAS  Google Scholar 

  • Salazar-Arredondo E, de Jesús Solís-Heredia M, Rojas-García E, Hernández-Ochoa I, Quintanilla-Vega B (2008) Sperm chromatin alteration and DNA damage by methyl-parathion chlorpyrifos and diazinon and their oxon metabolites in human spermatozoa. Reprod Toxicol 25:455–460

    Article  CAS  Google Scholar 

  • Sarabia L, Maurer I, Bustos-Obregón E (2009) Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on the mouse testis. Ecotoxicol Environ Saf 72:938–942

    Article  CAS  Google Scholar 

  • Sargazi Z, Nikravesh MR, Jalali M, Sadeghnia H, Anbarkeh FR, Mohammadzadeh L (2015) Gender-related differences in sensitivity to diazinon in gonads of adult rats and the protective effect of vitamin E. International Journal of Women’s Health and Reproduction Sciences 3(1):40–47

    Article  CAS  Google Scholar 

  • Shah MD, Iqbal M (2010) Diazinon-induced oxidative stress and renal dysfunction in rats. Food Chem Toxicol 48:3345–3353

    Article  CAS  Google Scholar 

  • Solberg Y, Belkin M (1997) The role of excitotoxicity in organophosphorous nerve agents central poisoning. Trends Pharmacol Sci 18:183–185

    Article  CAS  Google Scholar 

  • Tsitsimpikou C, Tzatzarakis M, Fragkiadaki P, Kovatsi L, Polychronis S, Kalogeraki A, Kouretas D, Tsatsakis AM (2013) Histopathological lesions, oxidative stress and genotoxic effects in liver and kidneys following long term exposure of rabbits to diazinon and propoxur. Toxicology 307:109–114

    Article  CAS  Google Scholar 

  • Yang H, Chung DH, Kim YB, Choi YH, Moon Y (2008) Ribotoxic mycotoxin deoxynivalenol induces G2/M cell cycle arrest via p21Cip/WAF1 mRNA stabilization in human epithelial cells. Toxicology 243(1–2):145–154

    Article  CAS  Google Scholar 

  • Yehia MA, El-Banna SG, Okab AB (2007) Diazinon toxicity affects histophysiological and biochemical parameters in rabbits. Exp Toxicol Pathol 59:215–225

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Ministère Tunisien de l’Enseignement Superieur et de la Recherche Scientifique et de la Technologie (Laboratoire de Recherche sur les Substances Biologiquement Compatibles, LRSBC). The authors are thankful to Mr. Hassen Bacha for his laboratory supports and constructive suggestions during the course of the study.

Author information

Authors and Affiliations

  1. Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, Rue Avicenne, 5000, Monastir, Tunisia

    Manel Boussabbeh, Intidhar Ben Salem, Mohamed Hamdi, Salsabil Ben Fradj, Salwa Abid-Essefi & Hassen Bacha

  2. Faculty of Sciences of Bizerte, Carthage University, Bizerte, Tunisia

    Manel Boussabbeh & Intidhar Ben Salem

Authors
  1. Manel Boussabbeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Intidhar Ben Salem
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed Hamdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Salsabil Ben Fradj
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Salwa Abid-Essefi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hassen Bacha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salwa Abid-Essefi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Responsible editor: Philippe Garrigues

Highlights

- DZ induces ROS generation in HCT116.

- DZ causes lipid peroxidation and the loss of mitochondrial membrane potential.

- DZ induces DNA fragmentation in HCT116.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Boussabbeh, M., Ben Salem, I., Hamdi, M. et al. Diazinon, an organophosphate pesticide, induces oxidative stress and genotoxicity in cells deriving from large intestine. Environ Sci Pollut Res 23, 2882–2889 (2016). https://doi.org/10.1007/s11356-015-5519-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-015-5519-y

Keywords

Search

Navigation