Alterations in Plasma and Tissue Acetylcholinesterase Activity Following Repeated Oral Exposure of Chlorpyrifos Alone and in Conjunction with Fluoride in Wistar Rats

  • Naseer Ahmad Baba
  • Rajinder Raina
  • Pawan Kumar VermaEmail author
  • Mudasir Sultana
Research Article


Concurrent exposures of more than one environmental contaminants are commonly encountered by human beings and animals. This study investigated the effect of chlorpyrifos alone and in conjunction with fluoride on plasma and tissue acetylcholinesterase (AChE) activity in wistar rats. Fluoride at 1 or 10 ppm in drinking water produced significant (P < 0.05) inhibition of AChE activity in a dose dependant manner and inhibition was maximum in brain (26.39 %) and least in heart (10.23 %). Similarly repeated oral administration of chlorpyrifos at 1 or 10 mg/kg produced a significant dose dependant inhibition of AChE activity (P < 0.05) which was observed maximum in brain (28.93 %) and least in heart (12.86 %). Co-exposure of chlorpyrifos and fluoride at higher doses produces more pronounced inhibition as compared to chlorpyrifos or fluoride exposed groups. Co-exposure produces maximum inhibition in erythrocyte (37.54 %) and least in plasma (18.26 %) of exposed animals as compared to control group. Observations from the present study suggested that co-exposure of fluoride and chlorpyrifos produces more pronounced inhibition of AChE than the individual exposure of either toxicant. Therefore the applications of chlorpyrifos as a pesticide should be reduced in areas where fluoride level in soil or ground water is high to avoid AChE inhibition.


Acetylcholinesterase Chlorpyrifos Fluoride Toxicity Wistar rats 


  1. 1.
    Ecbichon DJ (1996) Toxic effects of pesticides. In: Klaassen CD (ed) Casarett and Doull’s Toxicology. McGraw Hill, New Delhi, pp 643–675Google Scholar
  2. 2.
    Lotti M (2000) Organophosphorus compounds. In: Spencer PS, Schaumburg HH (eds) Experimental and clinical neurotoxicology, 2nd edn. Oxford University Press, New York, pp 898–925Google Scholar
  3. 3.
    Kiely T, Donaldson D, Grube A (2004) Pesticides industry sales & usage: 2000 & 2001 market estimates. U.S. Environmental Protection Agency.
  4. 4.
    Pope CN (1999) Organophosphorus pesticides: do they all have the same mechanism of toxicity. J Toxicol Environ Health Part B 2:101–121CrossRefGoogle Scholar
  5. 5.
    Bushnell PJ, Pope CN, Padilla S (1993) Behavioral and neurochemical effects of acute chlorpyrifos in rats: tolerance to prolonged inhibition of cholinesterase. J Pharmacol Exp Ther 266:1007–1017PubMedGoogle Scholar
  6. 6.
    Karanth S, Pope C (2003) Age-related effects of chlorpyrifos and parathion on acetylcholine synthesis in rat striatum. Neurotox Teratol 25:599–606CrossRefGoogle Scholar
  7. 7.
    Liu J, Pope CN (1996) Effects of chlorpyrifos on high-affinity choline uptake and hemicholinium-3 binding in rat brain. Fundam Appl Toxicol 34:84–90PubMedCrossRefGoogle Scholar
  8. 8.
    Vogelsberg V, Neff NH, Hadijiconstantinou M (1997) Cyclic AMP-mediated enhancement of high affinity choline transport and acetylcholine synthesis in brain. J Neurochem 68:1062–1070PubMedCrossRefGoogle Scholar
  9. 9.
    Won YK, Liu J, Olivier K, Zheng Q, Pope CN (2001) Age-related effects of chlorpyrifos on acetylcholine release in rat brain. Neurotoxicol 22:39–48CrossRefGoogle Scholar
  10. 10.
    Wu YJ, Harp P, Yan XR, Pope CN (2003) Nicotinic autoreceptor function in rat brain during maturation and aging: possible differential sensitivity to organophosphorus anti-cholinesterases. Chem Biol Interact 142:255–268PubMedCrossRefGoogle Scholar
  11. 11.
    Huff RA, Corcoran JJ, Anderson JK, Abou-Donia MB (1994) Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum. J Pharmacol Exp Ther 269:329–335PubMedGoogle Scholar
  12. 12.
    Katz LS, Marquis JK (1992) Organophosphate-induced alterations in muscarinic receptor binding and phosphoinositide hydrolysis in the human SK-N-SH cell line. Neurotoxicol 13:365–378Google Scholar
  13. 13.
    Liu J, Chakraborti T, Pope C (2002) In vitro effects of organophosphorus anticholinesterases on muscarinic receptor-mediated inhibition of acetylcholine release in rat striatum. Toxicol Appl Pharmacol 178:102–108PubMedCrossRefGoogle Scholar
  14. 14.
    Olivier JK, Liu J, Pope C (2001) Inhibition of forskolin-stimulated cAMP formation in vitro by paraoxon and chlorpyrifos oxon in cortical slices from neonatal, juvenile, and adult rats. J Biochem Mol Toxicol 15:263–269PubMedCrossRefGoogle Scholar
  15. 15.
    Zhang H, Liu J, Pope CN (2002) Age-related effects of chlorpyrifos on muscarinic receptor-mediated signaling in rat cortex. Arch Toxicol 75:676–684PubMedCrossRefGoogle Scholar
  16. 16.
    Zhavoronkov AA, Strochkova LS (1981) Fluorosis geographical pathology & some experimental findings. Fluoride 14:183–191Google Scholar
  17. 17.
    Yur F, Belge F, Mert N, Yoruk I (2003) Changes in erythrocyte parameters of fluorotic sheep. Fluoride 36:152–156Google Scholar
  18. 18.
    Wu ZJ, Ding JY, Qi DS, Yu YH (1995) Biochemical indexes of buffalo with fluorosis and their significance for diagnosis. J Huazhong Agric Univ 14:369–437Google Scholar
  19. 19.
    Kessabi M, Boudarine B, Braun JP, Lamnaruer D (1983) Serum biochemical effects of fluoride in sheep of the Darmous area. Fluoride 16:214–219Google Scholar
  20. 20.
    Hodge HC, Smith FA (1972) Fluoride in metallic contaminants and human health. Academic, New York, p 163Google Scholar
  21. 21.
    Voss G, Sachsse K (1970) Red cell and plasma cholinesterase activities in microsamples of human and animal blood determined simultaneously by a modified acetylcholine/DTNB procedure. Toxicol Applied Pharmacol 16:764–842CrossRefGoogle Scholar
  22. 22.
    Duncan DB (1955) Multiple range and multiple F tests. Biometrics 11:1–42CrossRefGoogle Scholar
  23. 23.
    Zhang JL, Qiao CL, Lan WS (2004) Detoxification of organophosphorus compounds by recombinant carboxylesterase from an insecticide-resistant mosquito and oxime-induced amplification of enzyme activity. Inc Environ Toxicol 19:154–159CrossRefGoogle Scholar
  24. 24.
    Khan AM, Sultana M, Raina R, Dubey N, Verma PK (2013) Effect of sub-acute oral exposure of Bifenthrin on biochemical parameters in crossbred goats. Proc Natl Acad Sci India Sect B. doi: 10.1007/s40011-012-0150-x Google Scholar
  25. 25.
    Khan AM, Sultana M, Raina R, Dubey N, Dar SA (2013) Effect of sub-acute toxicity of bifenthrin on antioxidant status and hematology after its oral exposure in Goats. Proc Natl Acad Sci India Sect B. doi: 10.1007/s40011-013-0157-y Google Scholar
  26. 26.
    Ola AK, Sandhu HS, Ranjan B, Dumka VK (2013) Fipronil-induced biochemical alterations during oral subacute toxicity in buffalo calves. Proc Natl Acad Sci India Sect B. doi: 10.1007/s40011-013-0167-9 Google Scholar
  27. 27.
    Nisar AN, Sultana M, Baba NA, Para PA, Waiz HA, Bhat SA, Zargar FA, Ahmad I (2013) Ameliorative effect of vitamin C on the haematological changes induced by exposure of chlorpyriphos and lead acetate in Wistar rats. Comp Clin Path. doi: 10.1007/s00580-013-1697-5 Google Scholar
  28. 28.
    Shanthakumari D, Srinivasalu S, Subramanian S (2004) Effect of fluoride intoxication on lipid peroxidation and antioxidant status in experimental rats. Toxicol 204:219–228CrossRefGoogle Scholar
  29. 29.
    Kant V, Srivastava AK, Verma PK, Raina R (2009) Alterations in the biochemical parameters during sub-acute toxicity of fluoride alone and in conjunction with aluminum sulphate in goats. Biol Trace Elem Res 130:20–30PubMedCrossRefGoogle Scholar
  30. 30.
    Gao Q, Liu Y, Guan Z (2009) Decreased learning and memory ability in rats with fluorosis: increased oxidative stress and reduced cholinesterase activity in the brain. Fluoride 42:277–285Google Scholar
  31. 31.
    Bhatnagar M, Rao P, Saxena A, Bhatnagar R, Meena P, Barbar S, Chouhan A, Vimal S (2006) Biochemical changes in brain and other tissues of young adult female mice from fluoride in their drinking water. Fluoride 39:280–284Google Scholar
  32. 32.
    Mehta A, Verma RS, Srivastava N (2005) Chlorpyrifos induced alterations in rat brain ACh E, lipid peroxidation and ATPases. Indian J Biochem Biophys 42:54–58PubMedGoogle Scholar
  33. 33.
    Verma RS, Mehta A, Srivastava N (2007) In vivo chlorpyrifos induced oxidative stress: attenuation by antioxidant vitamins. Pesticide Biochem Physiol 88:191–196CrossRefGoogle Scholar
  34. 34.
    Malkovics B, Szabo L, Ivan J, Gaal I (1983) Some further data on the effects of two organophosphate pesticides on the oxidative metabolism in the liver. Gen Pharmacol 14:689–769CrossRefGoogle Scholar

Copyright information

© The National Academy of Sciences, India 2014

Authors and Affiliations

  • Naseer Ahmad Baba
    • 1
  • Rajinder Raina
    • 1
  • Pawan Kumar Verma
    • 1
    Email author
  • Mudasir Sultana
    • 1
  1. 1.Division of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Sciences and Animal HusbandrySher-e-Kashmir University of Agricultural Sciences and Technology of JammuR S Pura, JammuIndia

Personalised recommendations