Skip to main content
Springer Nature Link
Log in

Evaluation of cytochrome c level and mitochondrial dysfunction biomarkers of Oryctolagus cuniculus liver exposed to Chlorpyrifos

  • Published:
Toxicology and Environmental Health Sciences Aims and scope Submit manuscript

Abstract

Organophosphate insecticides are increasingly used as substitutes for organochlorine and carbamate insecticides because of their high efficacity and lower persistence in the environment. Chlorpyrifos (CPF) (O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate), an organophosphate considered as one of the most widely used insecticides in agriculture worldwide. The aim of this work is to analyze oxidative stress after a chronic exposure per Os to two doses of CPF (375 ppm,750 ppm) and the effect on mitochondrial swelling and respiration and cytoplasmic Cyt c amount. Our results showed a little increase in the activity of mitochondrial GST, level of MDA and a decrease in GPx and CAT activity confirmed by the lack of O2 (respiration inhibition), GSH level in mitochondria. we found an increase in mitochondrial swelling with a significant decrease in respiratory level. The amount of escaped Cytochrome c from mitochondria was significantly increased in treated groups according to the control in doses-dependent manner. Finally, our study showed that Chlorpyrifos caused general mitochondrial dysfunction accompanied with elevated oxidative stress amount in rabbit’s liver.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Parakasam, A., Sethupathy, S. & Latitha, S. Plasma and RBCs antioxidant status in occupational mal pesticide sprayers. Clin. Chim. Acta. 310, 107–112 (2001).

    Article  Google Scholar 

  2. Geological, U. S. The quality of our nation’s waters -nutrients and pesticides, https://pubs.usgs.gov/circ/ 1999/1225/report.pdf (1999).

  3. US EPA. Reregistration eligibility science chapter for chlorpyrifos. Fate and environmental risk assessment chapter (Revised June), http://www.epa.gov/pesticides/ op/chlorpyrifos/efedrra1.pdf (2000).

  4. Minton, N. A. & Murray, V. S. G. A. Review of Organophosphate Poisoning. Med. Toxicol. Adverse Drug. Exp. 03, 350–375 (1988).

    CAS  Google Scholar 

  5. Casida, J. E. & Quistad, G. B. Organophosphate toxicity: Safety aspects of non-acetylcholinesterase secondary targets. Chem. Res. Tox. 17, 983–998 (2004).

    Article  CAS  Google Scholar 

  6. Muñoz-Quezada, M. T. et al. Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review. Int. J. Occup. Environ. Health. Apr. 29, 1–12 (2016).

    Google Scholar 

  7. Mackay, D. & Shiu, W.-Y. in Physical-chemical Properties and Environmental Fate Handbook (CRC Press LLC., U.S.A., 1999).

    Google Scholar 

  8. Khan, S. M. & Kour, G. Subacute oral toxicity of chlorpyrifos and the protective effect of green tea extract. Pest. Biochem. Phys. 89, 118–123 (2007).

    Article  CAS  Google Scholar 

  9. Rigterink, R. H. & Kenaga, E. E. Synthesis and Insecticidal Activity of Some O,O-Dialkyl 0-3,5,6-Trihalo-2-pyridyl Phosphates and Phosphorothioates. J. Agric. Food Chem. 14, 304–306 (1966).

    Article  Google Scholar 

  10. Sittig, M. in Handbook of Toxic and Hazardous Chemicals and Carcinogens 2nd Edn (eds Park Ridge N. J.) 581-582 (Noyes Publications, England and Wales, 1966).

  11. Cremlyn, R. J., Dewhurst, B. B., Wakeford, D. H. & Raja, R. A. Studies of organophosphorochloridates. VI. Reactions of steroid phosphorochloridates with amines and some alcohols. J. Chem. Soc. Perkin. 19, 1171–1179 (1972).

    Google Scholar 

  12. Slotkin, T. A., MacKillop, E. A., Ryde, I. T. & Seidler, F. J. Ameliorating the developmental neurotoxicity of chlorpyrifos: a mechanisms-based approach in PC12 cells. Environ. Health Perspect. 115, 1306–1313 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Slotkin, T. A. Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol. Appl. Pharmacol. 198, 132–151 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Slotkin, T. A., Levin, E. D. & Seidler, F. J. Compara tive developmental neurotoxicity of organophosphate insecticides: Effects on brain development are separable from systemic toxicity. Environ. Health. Perspect. 114, 746–751 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yoshikawa, T. & Naito, Y. What is oxidative stress? J. Japan Med. Assoc. 45, 271–276 (2002)

    Google Scholar 

  16. Yoshikawa, T. in Science of Free Radicals (Koudan Sha Saientifikku, Japan, 1997).

    Google Scholar 

  17. Cox, C. Chlorpyrifos, Part 2: human exposure. J. Pest. Ref. 15, 14–20 (1995).

    Google Scholar 

  18. Mitra, N. K., Siong, H. H. & Nadarajah, V. D. Evaluation of neurotoxicity of repeated dermal application of chlorpyrifos on hippocampus of adult mice. Ann. Agric. Env. Med. 15, 211–216 (2008).

    CAS  Google Scholar 

  19. Mehta, A., Verma, R. S. & Srivastava, N. Chlorpyrifosinduced alterations in the levels of hydrogen peroxide nitrate and nitrite in rat brain and liver. Pest. Biochem. Phys. 94, 55–59 (2009).

    Article  CAS  Google Scholar 

  20. Gultekin, F., Patat, S., Akca, M. & Akdogan, M. Melatonin can suppress the cytotoxic effect of chlorpyrifos on human Hep G2 cell lines. Hum. Exp. Tox. 35, 47–55 (2006).

    Article  Google Scholar 

  21. El-Shenawy, N. S. Effect of insecticides fenitrothion, endosulfan and abamectin on antioxidant parameters of isolated rat hepatocytes. In vitro Toxicol. 24, 1148–1157 (2010).

    Article  CAS  Google Scholar 

  22. Levine, R. L., Williams, J. A., Stadtman, E. R. & Shacter, E. Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol. 233, 346–357 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Stadtman, E. R. Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. Ann. Rev. Biochem. 62, 797–821 (1993).

    Article  CAS  PubMed  Google Scholar 

  24. Bebe, F. N. & Panemanogalore, M. Exposure of low doses of endosulfan and chlorpyrifos modifies endogenous antioxidants in tissues of rats. J. Env. Sci. Health. 38, 349–363 (2003).

    Article  Google Scholar 

  25. Verma, R. S., Mehta, A. & Srivastava, N. In vivo chlorpyrifos induced oxidative stress: attenuated by antioxidant vitamins. Pest. Biochem. Phys. 88, 191–196 (2007).

    Article  CAS  Google Scholar 

  26. Mansour, S. A. & Mossa, A. H. Oxidative damage, biochemical and histological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pest. Biochem. Physiol. 96, 14–23 (2010).

    Article  CAS  Google Scholar 

  27. Peccini, E., Staudenmann, W., Albergoni, V., Gabriel, R. D. & James, P. Purification and primary structure of metallothioneins induced by Cadmium in the protests Tetrahymena pigmentosa and Tetrahymena pyriformis. European J. Biochem. 226, 853–859 (1994).

    Article  Google Scholar 

  28. Masaya, M., Yoshinobu, H., Ai, Y., Maki, K. & Yasuo, O. Determination of cellular levels of nonprotein thiols in phytoplankton and their correlation with susceptibility to mercury. J. Phycol. 38, 983 (2002).

    Article  Google Scholar 

  29. Hopkin, S. P. in Handbook of ecotoxicology (eds Calow P) 397-427 (Blackwell, U.K., 1993).

  30. Franco, J. L. et al. Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase. Free Radic. Biol. Med. 47, 449–457 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Rouabhi, R., Gasmi, S., Boussekine, S. & Kebieche, M. Hepatic Oxidative Stress Induced by Zinc and Opposite Effect of Selenium in Oryctolagus cuniculus. J. Environ. Anal. Toxicol. 05, 289 (2015).

    Google Scholar 

  32. Carlson, K. & Ehrich, M. Organophophorus compoundinduced modification of SH-SY5Y human neuroblastoma mitochondrial transmembrane potential. Toxicol. Appl. Pharmacol. 160, 33–42 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. Tos-Luty, S. et al. Dermal and oral toxicity of Malathion in rats. Ann. Agric. Environ. Med. 10, 101–106 (2003).

    CAS  PubMed  Google Scholar 

  34. Boulassel, A. Evaluation of the toxicity of two drugs: Paracetamol and Ibuprofen, on a cellular model: Paramecium tetraurelia. Test on the subcellular scale. Doctorate thesis. Universite Badji Mokhtar de Annaba (2014).

    Google Scholar 

  35. Gasmi, S., Rouabhi, R. & Kebieche, M. Deltamethrine induced neurodegeneration and behavioral effect by dysfunction cytosolic antioxidant system in rats’ brain. Algerian J. Nat. Sci. 1, 14–22 (2016).

    Google Scholar 

  36. Taib, C. et al. Toxicity of Fe3O4 nanoparticles on oxidative stress status stromal enzymes and mitochondrial respiration and swelling of Oryctolagus cuniculus brain cortex. Toxicol. Environ. Health. Sci. 8, 349–355 (2016).

    Article  Google Scholar 

  37. Bebianno, M. J., Company, R., Serafim, A., Cosson, R. P. & Fiala-Medoni, A. Antioxidant systems and lipid peroxidation in Bathy-modiolusazoricus from Mid-Atlantic Ridge hydrothermal vent fields. Aquat. Toxicol. 75, 354–373 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Lopez, J. et al. Oxidative stress markers in surgically treated patients with refractory epilepsy. Clin. Biochem. 40, 292–298 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Halliwell, B., Gutteridge, J. M. Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet. 8391, 1396–1397 (1984).

    Article  Google Scholar 

  40. Beal, M. Mitochondrial dysfunction in neurodegenerative diseases. Biochem. Biophys. Acta. 1366, 211–223 (1998).

    CAS  PubMed  Google Scholar 

  41. Turner, K. J. et al. Altered gene expression during rat Wolffian duct development in response to in utero exposure to the antiandrogen linuron. Toxicol. Sci. 74, 114–128 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Rouabhi, R., Djebar-Berrebbah, H. & Djebar, M. R. Impact of Flufenoxuron, an IGR pesticide on Gallus domesticus embryonic development in ovo. J. Cell Anim. Biol. 2, 087–091 (2008).

    Google Scholar 

  43. Gu, Z. T. et al. Heat stress induced apoptosis is triggered by transcription-independent p53, Ca2+ dyshomeostasis and the subsequent Bax mitochondrial translocation. Sci. Rep. 5, doi:10.1038/srep11497 (2015).

  44. Zou, H., Li, Y., Liu, X. & Wang, X. An APAF-1 cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem. 274, 11549–11556 (1999).

    Article  CAS  PubMed  Google Scholar 

  45. Jevtic, G. et al. Mitochondrial impairment, apoptosis and autophagy in a rat brain as immediate and longterm effects of perinatal phencyclidine treatment in fluence of restraint stress. Prog. Neuropsychopharmacol. Biol. Psychiatry. 66, 87–96 (2016).

    Article  CAS  PubMed  Google Scholar 

  46. Fromenty, B. Toxicité mitochondriale et métabolique des médicaments. Réanimation 19, 552–567 (2010).

    Article  Google Scholar 

  47. Rachid, R., Houria, D. B. & Mohammed R. D. Impact of Flufenoxuron, an IGR pesticide on Gallus domesticus embryonic development in ovo. J. Cell Animal Biol. 2, 087–091 (2008).

    Google Scholar 

  48. Ming-Yuan, X. et al. Redox status in liver of rats following subchronic exposure to the combination of low dose dichlorvos and Deltamethrin. Pest. Biochem. Physiol. 124, 60–65 (2015).

    Article  Google Scholar 

  49. Ravagnan, L., Roumier, T. & Kroemer, G. Mitochondria the killer organelles and their weapons. J. Cell. Physiol. 192, 131–137 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Dayal, M. et al. Induction of Rat Brain Cytochrome P450s by Deltamethrin: Regional Specificity and Correlation with Neurobehavioral Toxicity. Neurotox. Res. 3, 351–357 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Yousef, M., Awad, T. & Mohamed, E. Deltamethrininduced oxidative damage and biochemical alterations in rat and its attenuation by Vitamin E. Toxicol. 227, 240–247 (2001).

    Article  Google Scholar 

  52. DiMauro, S. & Schon, E. A. Mitochondrial disorders in the nervous system. Ann. Rev. Neurosci. 31, 91–123 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Heiskanen, K. et al. Mitochondrial depolarization accompanies cytochrome c release during apoptosis. Biol. Chem. 274, 5654–5658 (1999).

    Article  CAS  Google Scholar 

  54. Bradford, M. A rapid and sensitive method for the quantities of microgram quantities of protein utilizing the principle of protein binding. Anal. Biochem. 72, 248–254 (1976).

    Article  CAS  PubMed  Google Scholar 

  55. Kristal, B. S., Park, B. K. & Yu, B. P. 4-hydroxynonénal est un puissant inducteur de la transition de perméabilité mitochondriale. J. Biol. Chem. 271, 6033–6038 (1996).

    Article  CAS  PubMed  Google Scholar 

  56. Rouabhi, R., Djebar-Berrebbah, H. & Djebar, M. R. Toxic Effect of a Pesticide, Diflubenzuron on Freshwater Microinvertebrate (Tetrahymena pyriformis). Chin. J. Appl. Environ. Biol. 12, 514–517 (2006).

    CAS  Google Scholar 

  57. Rouabhi, R., Djebar, H. & Djebar, M. R. Toxic Effects of Combined Molecule from Novaluron and Diflubenzuron on Paramecium caudatum. Am-Euras. J. Toxicol. 1, 74–80 (2009).

    Google Scholar 

  58. Weckbker, G. & Cory, J. G. Ribonucleotide reductase activity and growth of Glutathoine depleted mouse leukemia L1210 cells in vitro. Cancer Lett. 40, 257–264 (1988).

    Article  Google Scholar 

  59. Flohe, L. & Gunzler, W. A. Assays of glutathione peroxidase. Methods Enzymol. 105, 114–121 (1984).

    Article  CAS  PubMed  Google Scholar 

  60. Habig, H., Pabst, M. J. & Jokoby, W. B. Glutathione-S-transferase: the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249, 7130–7139 (1974).

    CAS  PubMed  Google Scholar 

  61. Cakmak, I. & Horst, W. J. Effect of aluminum on lipid peroxidation, superoxide dismutase, catalase, and peroxidase activities in root tips of soybean (Glycine max). Physiol. Plantarum. 83, 463–468 (1991).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Applied Biology department, Tebessa University, 12000, Tebessa, Algeria

    Nadjiba Toualbia, Rachid Rouabhi & Aya Salmi

Authors
  1. Nadjiba Toualbia
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Rachid Rouabhi
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Aya Salmi
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Rachid Rouabhi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Toualbia, N., Rouabhi, R. & Salmi, A. Evaluation of cytochrome c level and mitochondrial dysfunction biomarkers of Oryctolagus cuniculus liver exposed to Chlorpyrifos. Toxicol. Environ. Health Sci. 9, 325–331 (2017). https://doi.org/10.1007/s13530-017-0338-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13530-017-0338-9

Keywords