Subscribe Now Subscribe Today
Fulltext PDF
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

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.

Related Articles in ASCI
Similar Articles in this Journal
Search in Google Scholar
View Citation
Report Citation

  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


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  |  

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  |  

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

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.

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  |  

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.

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  |  

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

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.

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.

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  |  

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.

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

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  |  

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  |  

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.

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  |  

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.

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  |  

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

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  |  

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  |  

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  |  

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.

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.

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.
CrossRef  |  Direct Link  |  

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.

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

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.

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

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

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

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.

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.
CrossRef  |  Direct Link  |  

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.
PubMed  |  Direct Link  |  

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.

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.
CrossRef  |  PubMed  |  Direct Link  |  

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  |  

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.

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

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  |  

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  |  

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.

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  |  

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.

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

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  |  

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

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.

©  2019 Science Alert. All Rights Reserved
Fulltext PDF References Abstract