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  1. Journal of Biological Sciences
  2. Vol 4 (4), 2004
  3. 568-574
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Journal of Biological Sciences

Year: 2004 | Volume: 4 | Issue: 4 | Page No.: 568-574
DOI: 10.3923/jbs.2004.568.574
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Research Article

Rotenone-induced Parkinson`s Like Disease: Modulating Role of Coenzyme Q10

Hanan M. Abd-El Gawad, Dalaal M. Abdallah and Hanan S. El-Abhar

ABSTRACT


Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in the pathogenesis of Parkinson`s disease (PD). Because of the potential role of mitochondrial dysfunction in striatal neurodegeneration in PD, rotenone, a potent reversible competitive inhibitor of complex I, was chosen as a possible trigger of Parkinson`s-like syndrome. The loss of dopaminergic neurons in PD, besides the blockade of mitochondrial complexes, augment the formation of free radicals. Therefore, administration of the mitochondrial enhancer coenzyme Q10 (CoQ10), with its known antioxidant activity, may be promising in attenuating the case. Male Wistar albino rats (250-300 g) were allocated into a normal control group, rotenone-induced toxicity group and rotenone + CoQ10-treated group. Rotenone was injected s.c at a dose of 1.5 mg kg-1 every other day for a total of six injections. CoQ10 was administered orally at a dose of 100 mg kg-1 day -1 starting from the first day of rotenone injection and continued thereafter for a total period of 11 days. The striatal biochemical parameters were assessed 24 h after the last rotenone injection. Rotenone resulted in significant decrease in the contents of dopamine (DA), glutamate and reduced glutathione (GSH) accompanied by a marked increase in malondialdehyde (MDA) level and lactate dehydrogenase (LDH) activity. However, no change was observed in the levels of superoxide dismutase (SOD) and nitric oxide (nitrite/nitrate). CoQ10 reduced the elevated levels of MDA and LDH, while restored that of GSH. However, the activity of SOD enzyme was stimulated. In conclusion, this study indicated the role of CoQ10 in ameliorating the oxidative stress associated with PD, but it was not capable of overcoming the whole negative effects of rotenone. Therefore, new approaches besides providing antioxidants that offer neuroprotection of striatal dopaminergic neurons in PD are still in need.
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How to cite this article

Hanan M. Abd-El Gawad, Dalaal M. Abdallah and Hanan S. El-Abhar, 2004. Rotenone-induced Parkinson`s Like Disease: Modulating Role of Coenzyme Q10. Journal of Biological Sciences, 4: 568-574.

DOI: 10.3923/jbs.2004.568.574

URL: https://scialert.net/abstract/?doi=jbs.2004.568.574

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REFERENCES


  1. Fahn, S., 2003. Description of Parkinson's disease as a clinical syndrome. Ann. N. Y. Acad. Sci., 991: 1-14.
    CrossRef

  2. Olanow, C.W. and W.G. Tatton, 1999. Etiology and pathogenesis of parkinson's disease. Annu. Rev. Neurosci., 22: 123-144.
    PubMed

  3. De Silva H.R., N.L. Khan and N.W. Wood, 2000. The genetics of parkinson's disease. Curr. Opin. Genet. Dev., 10: 292-298.

  4. Duan, W., B. Ladenheim, R.G. Cutler, I.I. Kruman, J.L. Cade and M.P. Mattson, 2002. Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of parkinson's disease. J. Neurochem., 80: 101-110.

  5. Gao, H.M., J.S. Hong, W. Zhang and B. Liu, 2002. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J. Neurosci., 22: 782-790.

  6. Betarbet, R., T.B. Sherer, G. MacKenzie, M.G. Osuna, A.V. Panov and J.T. Greenamyre, 2000. Chronic systemic pesticide exposure reproduces features of parkinson's disease. Nature Neurosci., 3: 1301-1306.
    PubMed

  7. Le Couteur, D.G., A.J. McLean, M.C. Taylor, B.L. Woodham and P.G. Boar, 1999. Pesticides and Parkinson's disease. Biomed. Pharmacother., 53: 122-130.
    CrossRefDirect Link

  8. Haley, T.J., 1978. A review of the literature of rotenone. J. Environ. Pathol. Toxicol., 1: 315-317.

  9. Gutman, M., T.P. Singer, H. Beinert and J.E. Casida, 1970. Reaction sites of rotenone, piericidin A and amytal in relation to the nonheme iron components of NADH dehydrogenase. Proc. Nat. Acad. Sci. USA., 65: 763-770.

  10. Jenner, P., 2001. Parkinson's disease, pesticides, mitochondrial dysfunction. Trends Neurosci., 24: 245-247.

  11. Cassarino, D.S., C.P. Fall, R.H. Swerdlow and J.P. Jr. Bennett, 1997. Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of parkinson's disease. Biochem. Biophys. Acta, 1362: 77-86.

  12. Muller, T., T. Buttner, A.F. Gholipour and W. Kuhn, 2003. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with parkinson's disease. Neurosci. Lett., 341: 201-204.

  13. Jenner, P.and C.W. Olanow, 1998. Understanding cell death in parkinson's disease. Ann. Neurol., 44: 72-84.
    PubMed

  14. Ebadi, M., S.K. Srinivasan and M.D. Bax, 1996. Oxidative stress and antioxidant therapy in parkinson's disease. Prog. Neurobiol., 48: 1-19.
    CrossRef

  15. Ferrante, R.J., J.B. Schultz, N.W. Kowall and M.F. Beal, 1997. Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not substantia nigra. Brain Res., 753: 157-162.
    CrossRef

  16. Frei, B., M.C. Kim and B.N. Ames, 1990. Ubiquinol-10 is an effective lipid-soluble antioxidant at physiological concentrations. Proc. Nat. Acad. Sci. USA., 87: 4879-4883.
    Direct Link

  17. Abe, K., H. Fujimura, Y. Nishikawa, S. Yorifuki and T. Mezaki et al., 1991. Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Acta Neurol. Scand, 83: 356-359.
    CrossRef

  18. Beal, M.F., D.R. Henshaw, B.G. Jenkins, B.R. Rosen and J.B. Schulz, 1994. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann. Neurol., 36: 882-888.
    CrossRefDirect Link

  19. Beal, M.F., R.T. Mattews, A. Tieleman and C.W. Shults, 1998. Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res., 783: 109-114.

  20. Thiffault, C., J.W. Langston and D.A. di Monte, 2000. Increased striatal dopamine turnover following acute administration of rotenone to mice. Brain Res., 885: 283-288.

  21. Ciarlone, A.E. and M.S. Juras, 1981. Lidocaine and procaine alter rat brain amines. J. Dent. Res., 60: 1886-1890.

  22. Tracey, W.R., J. Tse and G. Carter, 1995. Lipopolysaccharide-induced changes in plasma nitrite and nitrate concentrations in rats and mice: Pharmacological evaluation of nitric oxide synthase inhibitors. J. Pharmacol. Exp. Ther., 272: 1011-1015.

  23. Grandati, M., C. Verrecchia, M.L. Revaud, M. Allix, R.G. Boulu and M. Plotkine, 1997. Calcium-independent NO-synthase activity and nitrites/nitrates production in transient focal cerebral ischemia in mice. Br. J. Pharmacol., 122: 625-630.

  24. Beutler, E., O. Duron and B.M. Kelly, 1963. Improved method for the determination of blood glutathione. J. Lab. Clin. Med., 61: 882-888.
    PubMedDirect Link

  25. Uchiyama, M. and M. Mihara, 1978. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem., 86: 271-278.
    CrossRefDirect Link

  26. Marklund, S. and G. Marklund, 1974. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem., 47: 469-474.
    CrossRefPubMedDirect Link

  27. Buhl, S.N. and K.Y. Jackson, 1978. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30 and 37°C. Clin. Chem., 24: 828-831.

  28. Lowry, O.H., N.J. Rosebrough, A.L. Farr and R.J. Randall, 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem., 193: 265-275.
    CrossRefPubMedDirect Link

  29. Helmuth, L., 2000. Neuroscience: Pesticide causes parkinson's in rats. Science, 290: 1068-1068.

  30. Heikkila, R.E., W.J. Nicklas, I. Vyas and R.C. Duvoisin, 1985. Dopaminergic toxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats: Implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Neurosci. Lett., 62: 389-394.

  31. Kim, W.G., R.P. Mohney, B. Wilson, G.H. Jeohn, B. Liu and J.S. Hong, 2000. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: Role of microglia. J. Neurosci., 20: 6309-6316.

  32. Wilson, J.X., 1997. Antioxidant defeanse of the brain: A role for astrocytes. Can. J. Physiol. Pharmacol., 75: 1149-1163.

  33. Zhan, H., R.K. Gupta, J. Weaver and S. Pollack, 1990. Iron bound to low MW ligands: Interactions with mitochondria and cytosolic proteins. Eur. J. Haematol., 44: 125-131.

  34. Waterfall, A.H., G. Singh, J.R. Fry and C.A. Marsden, 1996. Acute acidosis elevates malondialdehyde in rat brain in vivo. Brain Res., 712: 102-106.
    CrossRef

  35. Dexter, D.T., C.J. Carter, F.R. Wells, F. Javoy-Agid and Y. Agid et al., 1989. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J. Neurochem., 52: 381-389.
    Direct Link

  36. Ciesielska, A., I. Joniec, A. Przybylkowski, G. Gromadzka, I. Kurkowska-Jastrzebska, A. Czlonkowska and A. Czlonkowski, 2003. Dynamics of expression of the mRNA for cytokines and inducible nitric synthase in a murine model of the Parkinson's disease. Acta Neurobiol. Exp. Wars., 63: 117-126.
    Direct Link

  37. Cutillas, B., M. Espejo and S. Ambrosio, 1998. 7-Nitroindazole prevents dopamine depletion caused by low concentrations of MPP+ in rat striatal slices. Neurochem. Int., 33: 35-40.
    PubMed

  38. Thiffault, C., N. Aumont, R. Quirion and J. Poirier, 1995. Effect of MPTP and L-deprenyl on antioxidant enzymes and lipid peroxidation levels in mouse brain. J. Neurochem., 65: 2725-2733.
    CrossRef

  39. Saggu, H., J. Cooksey, D. Dexter, F.R. Wells, A. Lees, P. Jenner and C.D. Marsden, 1989. A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra. J. Neurochem., 53: 692-697.
    CrossRef

  40. Marttila, R.J., H. Lorentz and U.K. Rinne, 1988. Oxygen toxicity protecting enzymes in Parkinson's disease. Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. J. Neurol. Sci., 86: 321-331.
    CrossRef

  41. Gsell, W., R. Conrad, M. Hickethier, E. Sofic and L. Frolich et al., 1995. Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type. J. Neurochem., 64: 1216-1223.
    CrossRefDirect Link

  42. Beal, M.F., 2002. Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic. Res., 36: 455-460.
    CrossRefDirect Link

  43. Schulz, J.B., R.T. Matthews, D.R. Henshaw and M.F. Beal, 1996. Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: Implications for neurodegenerative diseases. Neuroscience, 71: 1043-1048.
    CrossRef

  44. Beal, M.F., E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller et al., 1993. Neurochemical and histologic characterization of excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci., 13: 4181-4192.
    Direct Link

  45. Favit, A., F. Nicoletti, U. Scapagnini and P.L. Canonico, 1992. Ubiquinone protects cultured neurons against spontaneous and excitotoxin-induced degeneration. J. Cerebr. Blood Flow Metab., 12: 638-645.
    PubMed

  46. Barbiroli, B., S. Lotti and R. Lodi, 1999. Improved brain and muscle mitochondrial respiration with CoQ. An in vivo study by 31P-MR spectroscopy in patients with mitochondrial cytopathies. Biofactors, 9: 253-260.
    PubMed

  47. Brouillet, E., D.R. Henshaw, J.B. Schulz and M.F. Beal, 1994. Aminoacetic acid striatal lesions attenuated by 1,3-butanediol and coenzyme Q10. Neurosci. Lett., 177: 58-62.

  48. Carrillo, M.C., K. Kitani, S. Kanai, Y. Sato and G.O. Ivy, 1992. The ability of (-) deprenyl to increase superoxide dismutase activities in the rat is tissue and brain region selective. Life Sci., 50: 1985-1992.
    CrossRef

  49. Lund, P., 1990. L-Glutamine and L-glutamate UV-Method with Glutaminase and Glutamate Dehydrogenase. In: Methods of Enzymatic Analysis, Bergmeyer, H.S., J. Bergmeyer and M. Grasl (Eds.). Vol. VIII, Springer-Verlag, Weinheim, Germany, pp: 357.

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