Neurotoxicity Research

, Volume 21, Issue 4, pp 345–357 | Cite as

Protective Efficacy of Coenzyme Q10 Against DDVP-Induced Cognitive Impairments and Neurodegeneration in Rats

  • B. K. Binukumar
  • Nidhi Gupta
  • Aditya Sunkaria
  • Ramesh Kandimalla
  • W. Y. Wani
  • D. R. Sharma
  • Amanjit Bal
  • Kiran Dip GillEmail author


The present study was carried out to elucidate the effects of coenzyme Q10 (CoQ10) against cognitive impairments induced by dichlorvos (DDVP). We have previously shown organophosphate, DDVP-induced impairments in neurobehavioral indices viz. rota rod, passive avoidance, and water maze tests. In addition to this, we have also reported that chronic DDVP exposure leads to decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I–III activity. Administration of CoQ10 (4.5 mg/kg, i.p. for 12 weeks prior to DDVP administration daily) to DDVP-treated rats improved cognitive performance in passive avoidance task and Morris water maze test. Furthermore, CoQ10 treatment also reduced oxidative stress (as evident by reduced malondialdehyde, decreased ROS and increased Mn-SOD activity) in DDVP-treated rats’ hippocampus region, along with enhanced activity of complexes I–III and complex IV. Electron microscope studies of rat hippocampus mitochondria revealed that CoQ10 administration leads to near normal physiology of mitochondria with well-defined cristae compared with DDVP-treated animals where enlarged mitochondria with distorted cristae are observed. CoQ10 administration also attenuated neuronal damage in hippocampus as evident from histopathological studies. These results demonstrate the beneficial effects of CoQ10 against organophosphate-induced cognitive impairments and hippocampal neuronal degeneration.


Organophosphate Acetylcholinesterase DDVP Memory Oxidative damage 



This study has been supported by Indian Council of Medical Research, India, in the form of SRF to Binukumar BK.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Atlante A, Gagliardi S, Marra E, Calissano P (1998) Neuronal apoptosis in rats is accompanied by rapid impairment of cellular respiration and is prevented by scavengers of reactive oxygen species. Neurosci Lett 245:127–130PubMedCrossRefGoogle Scholar
  2. Benoit IG, Lee VM-Y (2000) A new link between pesticides and Parkinson’s disease. Nat Neurosci 3:1227–1228CrossRefGoogle Scholar
  3. Beretta S, Sala G, Mattavelli L, Ceresa C, Casciati A, Ferri A, Carrì MT, Ferrarese C (2003) Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by N-acetylcysteine. Neurobiol Dis 13:213–221PubMedCrossRefGoogle Scholar
  4. Beyer RE (1996) The role of ascorbate in antioxidant protection of biomembranes: inter-action with vitamin E and coenzyme Q. J Bioenerg Biomembr 26:349–358CrossRefGoogle Scholar
  5. Beyer RE, Segura-Aguilar J, Di Bernardo S, Cavazzoni M, Fato R, Fiorentini D, Galli MC, Setti M, Landi L, Lenaz G (1996) The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems. Proc Natl Acad Sci USA 93:2528–2532PubMedCrossRefGoogle Scholar
  6. Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK (2002) Glutathione, iron and Parkinson’s disease. Biochem Pharmacol 64:1037–1048PubMedCrossRefGoogle Scholar
  7. Binukumar BK, Bal A, Kandimalla R, Sunkaria A, Gill KD (2010) Mitochondrial energy metabolism impairment and liver dysfunction following chronic exposure to dichlorvos. Toxicology 270(2–3):77–84PubMedCrossRefGoogle Scholar
  8. Chen CM, Yin MC, Hsu CC, Liu TC (2007) Antioxidative and anti-inflammatory effects of four cysteine-containing agents in striatum of MPTP-treated mice. Nutrition 23:589–597PubMedCrossRefGoogle Scholar
  9. Cleren C, Yang L, Lorenzo B, Calingasan NY, Schomer A, Sireci A, Wille EJ, Beal MF (2008) Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism. J Neurochem 104:1613–1621PubMedCrossRefGoogle Scholar
  10. De Bustos F, Molina JA, Jimenez–Jimenez FJ, Garcia-Redondo A, Gomez-Escalonilla C, Porta-Etessam J (2000) Serum levels of coenzyme Q10 in patients with Alzheimer’s disease. J Neural Transm 107(2):233–239PubMedCrossRefGoogle Scholar
  11. Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 24:95–204Google Scholar
  12. Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM (2002) Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington’s disease. J Neurosci 22:1592–1599PubMedGoogle Scholar
  13. Grieb P, Ryba MS, Sawicki J, Chrapusta SJ (1997) Oral coenzyme Q10 administration prevents the development of ischemic brain lesions in a rabbit model of symptomatic vasospasm. Acta Neuropathol (Berl) 94(4):363–368CrossRefGoogle Scholar
  14. Guillette EA, Meza M, Aquilar MG, Soto AD, Garcia IE (1998) An anthropological approach to the evaluation of preschool children exposed to pesticides in Mexico. Environ Health Perspect 106:347–353PubMedCrossRefGoogle Scholar
  15. Kaur P, Radotra Bishan, Minz Ranjana, Gill KD (2007) Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic DDVP (OP) exposure in rat brain. NeuroToxicology 28:1208–1219PubMedCrossRefGoogle Scholar
  16. King TE, Howard RL (1967) Preparation and properties of soluble NADH dehydrogenase from cardiac muscle. In: Colowick SP, Kaplan NO (eds) Methods in enzymology. Academic Press, New York, pp 275–276Google Scholar
  17. Kochs E, Werner C (1995) Neuroprotection: fact or fantasy? Eur J Anaesthesiol 10(Suppl.):67–70Google Scholar
  18. Kumar V, Bal A, Gill KD (2009) Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage. Toxicology 255:117–123PubMedCrossRefGoogle Scholar
  19. Levin ED, Addy N, Baruah A, Elias A, Christopher NC, Seidler FJ (2002) Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations. Neurotoxicol Teratol 24:733–741PubMedCrossRefGoogle Scholar
  20. Li H, Klein G, Sun P, Buchan AM (2000) CoQ10 fails to protect brain against focal and global ischemia in rats. Brain Res 877(1):7–11PubMedCrossRefGoogle Scholar
  21. Lodi R, Iotti S, Scorolli L, Scorolli L, Bargossi AM, Sprovieri L, Zaniol P, Meduri R, Barbiroli B (1994) The use of phosphorus magnetic resonance spectroscopy to study in vivo the effect of coenzyme Q10 treatment in retinitis pigmentosa. Mol Aspects Med 15(suppl.):221–230CrossRefGoogle Scholar
  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin–phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  23. MacMillan-Crow LA, Crow JP, Kerby JD, Beckman JS, Thompson JA (1966) Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proc Natl Acad Sci USA 93:11853–11858CrossRefGoogle Scholar
  24. Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998) Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci USA 95(15):8892–8897PubMedCrossRefGoogle Scholar
  25. Morris RGM (1984) Development of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60PubMedCrossRefGoogle Scholar
  26. Nelson LM (1995) Epidemiology of ALS. Clin Neurosci 3:327–331PubMedGoogle Scholar
  27. Okamoto F, Allen BS, Buckberg GD (1986) Reperfusate composition: supplemental role of intravenous and intracoronary coenzyme Q10 in avoiding reperfusion damage. J Thorac Cardiovasc Surg 92:573PubMedGoogle Scholar
  28. Ostrowski RP (1999) Effect of coenzyme Q10 (CoQ10) on superoxide dismutase activity in ET-1 and ET-3 experimental models of cerebral ischemia in the rat. Folia Neuropathol 37(4):247–251PubMedGoogle Scholar
  29. Ostrowski RP (2000) Effect of coenzyme Q(10) on biochemical and morphological changes in experimental ischemia in the rat brain. Brain Res Bull 53(4):399–407PubMedCrossRefGoogle Scholar
  30. Piala JJ, High JP, Hessert JLJ, Burke JC, Crower BN (1959) Pharmacological and acute toxicological comparisons of trifluoropromazine and chlorpromazine. J Pharmacol Exp Ther 127:55–65PubMedGoogle Scholar
  31. Ray DE, Richards PG (2004) The potential for toxic effects of chronic, low-dose exposure to organophosphates. Toxicol Teratol 120:343–351Google Scholar
  32. Reed JC, Jurgensmeyer JM, Matsuyama S (1998) Bcl-2 family proteins and mitochondria. Biochim Biophys Acta 366:127–137Google Scholar
  33. Shults CW, Haas RH, Passov D, Beal MF (1997) Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol 42:261–264PubMedCrossRefGoogle Scholar
  34. Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S et al (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59(10):1541–1550PubMedCrossRefGoogle Scholar
  35. Shults CW, Haas R, Oakes D, Kieburtz K, Plumb S, Shoulson I et al (2004) Measuring the effects of therapy in Parkinson disease. JAMA 291(20):2430–2431PubMedCrossRefGoogle Scholar
  36. Sohmiya M, Tanaka M, Tak NW, Yanagisawa M, Tanino Y, Suzuki Y et al (2004) Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson’s disease. J Neurol Sci 223:161–166PubMedCrossRefGoogle Scholar
  37. Somayajulu-Niţu M, Sandhu JK, Sikorska M, Sridhar TS, Matei A (2009) Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10. BMC Neurosci 10(88):1–12Google Scholar
  38. Sottocasa GL, Kuylenstierna B, Ernster L, Bergstrand A (1967) An electron transport system associated with the outer membrane of liver mitochondria. J Cell Biol 32:415–438PubMedCrossRefGoogle Scholar
  39. Steenland K (1996) Chronic neurological effects of organophosphate pesticides. Br Med J 312:1312–1313CrossRefGoogle Scholar
  40. Terry AV Jr, Stone JD, Buccafusco JJ, Sickles DW, Sood A, Prendergast MA (2003) Repeated exposures to subthreshold doses of chlorpyrifos in rats: Hippocampal damage, impaired axonal transport, and deficits in spatial learning. J Pharmacol Exp Ther 305:375–384PubMedCrossRefGoogle Scholar
  41. Tsukahara Y, Wakatsuki A, Okatani Y (1999) Antioxidant role of endogenous coenzyme Q against the ischemia and reperfusion-induced lipid peroxidation in fetal rat brain. Acta Obstet Gynecol Scand 78(8):669–674PubMedCrossRefGoogle Scholar
  42. Verma SK, Raheja G, Gill KD (2009) Role of muscarinic signal transduction and CREB phosphorylation in dichlorvos-induced memory deficits in rats: an acetylcholine independent mechanism. Toxicology 256(3):175–182PubMedCrossRefGoogle Scholar
  43. Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2:32–328CrossRefGoogle Scholar
  44. Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. J Biochem 99:667–676Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • B. K. Binukumar
    • 1
  • Nidhi Gupta
    • 1
  • Aditya Sunkaria
    • 1
  • Ramesh Kandimalla
    • 1
  • W. Y. Wani
    • 1
  • D. R. Sharma
    • 1
  • Amanjit Bal
    • 2
  • Kiran Dip Gill
    • 1
    Email author
  1. 1.Department of BiochemistryPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of HistopathologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

Personalised recommendations