Coenzyme Q10 Abrogated the 28 Days Aluminium Chloride Induced Oxidative Changes in Rat Cerebral Cortex


Affiliations

  • Bombay College of Pharmacy, Department of Pharmacology, Mumbai, Maharashtra, India

Abstract

Objective: The present study was designed to elucidate the impact of oral administration of aluminium chloride for 28 days with respect to oxidative stress in the cerebral cortex of female rats. Further, to investigate the potentials of Coenzyme (Co) Q10 (4, 8, and 12 mg/kg, i.p.) in mitigating the detrimental changes. Materials and Methods: Biochemical estimations of cerebral lipid peroxidation (LPO), reduced glutathione (GSH), vitamin E and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were carried out after 28 days of aluminium chloride (AlCl3) and Co Q10 exposures along with histopathological examination of cerebral cortex of the rats. Results: Subacute exposure to AlCl3 (5 mg/kg) led to significant decrease in levels of GSH, vitamin E and activities of SOD, CAT, GPx, and an increase in LPO of cerebral cortex. These aberrations were restored by Co Q10 (12 mg/kg, i.p.). This protection offered was comparable to that of L‑deprenyl (1 mg/ kg, i.p.) which served as a reference standard. Histopathological evaluations confirmed that the normal cerebral morphology was maintained by Co Q10. Conclusion: Thus, AlCl3 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in cerebral cortex of female Wistar rats. Supplementation with intraperitoneal Co Q10 abrogated these deleterious effects of AlCl3.

Keywords

Aluminium chloride, coenzyme Q10, L‑deprenyl, neurotoxicity, oxidative stress

Full Text:

References

Al Ahmad A, Gassmann M, Ogunshola OO. Involvement of oxidative stress in hypoxia induced blood brain barrier break down. Microvasc Res 2012;84:222‑5.

Uttara B, Singh AV, Zamboni P. Mahajan RT. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmcol 2009;7:65‑74.

Cannon JR, Greenamyre JT. The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol Sci 2011;124:225‑50.

Wright DA, Welbourn PM. Environmental Toxicology. Cambridge University Press series publication. 1st ed. 2002. p. 70.

Marrugo‑Negrete J, Verbel JO, Ceballos EL, Benitez LN. Total mercury and methylmercury concentrations in fish from the Mojana region of Colombia. Environ Geochem Health 2008;30:21‑30.

Monnet‑Tschudi F, Zurich MG, Boschat C, Corbaz A, Honegger P. Involvement of environmental mercury and lead in the etiology of neurodegenerative diseases. Rev Environ Health 2006;21:105‑18.

Wormser U, Brodsky B, Milatovic D, Finkelstein Y, Farina M, Rocha JB, et al. Protective effect of a novel peptide against methylmercury‑induced toxicity in rat primary astrocytes. Neurotoxicology 2012;33:763‑68.

Lobo Torres LH, Moreira WL, Tamborelli Garcia RC, Annoni R, Nicoletti Carvalho AL, Teixeira SA, et al. Environmental tobacco smoke induces oxidative stress in distinct brain regions of infant mice. J Toxicol Environ Health A 2012;75:971‑80.

Yokel RA, McNamara PJ. Aluminium toxicokinetics: An updated minireview. Pharmacol Toxicol 2001;88:159‑67.

Slanina P, French W, Ekstrom LG, Lööf L, Slorach S, Cedergren A. Dietary citric acid enhances absorption of aluminum in antacids. Clin Chem 1986;32:539‑41.

Harris WR, Berthon G, Day JP, Exley C, Flaten TP, Forbes WF, et al. Speciation of aluminium in biological systems. J Toxicol Environ Health 1996;48:543‑68.

Kong S, Liochev S, Fridovich I. Aluminum (III) facilitates the oxidation of NADH by the superoxide anion. Free Radic Biol Med 1992;13:79‑81.

Szutowicz A. Aluminium NO, and nerve growth factor neurotoxicity in cholinergic neurons. J Neurosci Res 2001;66:1009‑18.

Nayak P. Aluminum: Impacts and disease. Environ Res 2002;89:101‑15.

Powell AK, Heath SL. X‑ray structural analysis of biological relevant aluminium (III) complexes. Coordination Chem Rev 1996;149:59‑80.

Bihagi SW, Sharma M, Singh AP, Tiwari M. Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain. J Ethnopharmacol 2009;124:409‑15.

McDermott JR, Smith AI, Iqbal K, Wisniewski HM. Brain aluminium in aging and Alzheimer disease. Neurology 1979;29:809‑14.

Yokel RA. Blood‑brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal‑induced neurodegeneration. J Alzheimers Dis 2006;10:223‑53.

Ackley DC, Yokel RA. Aluminium citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood/brain barrier. Toxicology 1997;120:89‑97.

Yokel RA, Allen DD, Ackley DC. The distribution of aluminium into and out of the brain. J Inorg Biochem 199;76:127‑32.

Kumar NS, Agrawal P, Sujata AS, Bhavana BK. Fermentation, media optimization studies for Coenzyme Q10 production by Saccharomyces cerevisiae. Int Res J Pharm 2012;3:132‑8.

Beal F. Therapeutic effects of coenzyme Q10 in neurodegenerative diseases. Methods Enzymol 2006;382:473‑87.

Bentiger M, Brismar K, Dallner G. The antioxidant role of coenzyme Q. Mitochondrion 2007;7:S41‑50.

Crane FL. Discovery of ubiquinone (coenzyme Q) and an overview of function. Mitochondrion 2007;7:S2‑7.

Borekova M, Hojerova J, Koprda V, Bauerova K. Nourishing and health benefits of coenzyme Q10‑a review. Czech J Food Sci 2008;26:229‑41.

Turunen M, Olssan J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004;1660:171‑99.

Santos GC, Antunes LM, Santos AC, Maria LP. Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases. Braz J Pharm Sci 2009;45:607‑18.

Tina K. Coenzyme Q10 in Parkinson’s disease: Ready for first line use? Nat Med J 2010;2:3‑7.

Todd KG, Butterworth RF. Increased neuronal cell survival after L‑deprenyl treatment in experimental thiamine deficiency. J Neurosci Res 1998;52:240‑6.

Binukumar BK, Gupta N, Bal A, Gill KD. Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal death by chronic Coenzyme Q10 pretreatment. Toxicol Appl Pharmacol 2011;256:73‑82.

Ohkawa H, Onishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351‑8.

Moron MS, Depierre JW. Mannervik B. Levels of glutathione, glutathione reductase and glutathione S‑transferase activities in rat lung and liver. Biochim Biophys Acta 1979;582:67‑78.

Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol 1984;105:138‑47.

Beers RF Jr, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase.J Biol Chem 1952;195:133‑40.

Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem 1978;90:81‑9.

Carrillo MC, Kanai S, Nokubo M. Kitani K. Deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci 1991;48:517‑21.

Culling CF. Handbook of histopathological and histochemical techniques: (including museum techniques): Butterworth. 3rd ed.1974. p. 361.

Sathyasaikumar KV, Swapna I, Reddy PV, Murthy CR, Dutta GA, Senthilkumaran B, et al. Fulminant hepatic failure in rats induces oxidative stress differentially in cerebral cortex, cerebellum and pons medulla. Neurochem Res 2007;32:517‑24.

Onodera K, Omoi NO, Fukui K, Hayasaka T, Shinkai T, Suzuki S, et al. Oxidative damage of rat cerebral cortex and hippocampus, and changes in antioxidative defense systems caused by hyperoxia. Free Radic Res 2003;37:367‑72.

Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S. Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann N Y Acad Sci 2000;928:169‑73.

Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Nati Acad Sci U S A 1998;95:8892‑7.

Chaturvedi RK, Beal MF. Mitochondrial approaches for neuroprotection. Ann N Y Acad Sci 2008;1147:395‑412.

Mounsey RB, Teismann P. Mitochondrial dysfunction in Parkinson’s disease: Pathogenesis and neuroprotection. Parkinson’s Dis 2010;2011:617472.

Koppula S, Kumar H, More SV, Kim BW, Kim IS, Choi DK. Recent advances on the neuroprotective potential of antioxidants in experimental models of Parkinson’s disease. Int J Mol Sci 2012;13:10608‑29.

Elipenahli C, Stack C, Jainuddin S, Gerges M, Yang L, Starkov A, et al. Behavioral improvement after chronic administration of coenzyme Q10 in P301S transgenic mice. J Alzheimers Dis 2012;28:173‑82.

Rauscher FM, Sanders RA, Watkins JB 3rd. Effects of coenzyme Q10 treatment on antioxidant pathways in normal and streptozotocin‑induced diabetic rats. J Biochem Mol Toxicol 2011;15:41‑6.

Muralikrishnan D, Samantaray S, Mohanakumar KP. Ddeprenyl protects nigrostriatal neurons against 1‐methyl‐4‐ phenyl‐1, 2, 3, 6‐tetrahydropyridine‐induced dopaminergic neurotoxicity. Synapse 2003;50:7‑13.

Ebadi M, Sharma S, Shavali S, Sangchot P, Brekke L. The multiple actions of selegiline. Proc West Pharmacol Soc 2002;45:39‑41.

Jyoti A, Sethi P, Sharma D. Bacopa monniera prevents from aluminium neurotoxicity in the cerebral cortex of rat brain.J Ethnopharmacol 2007;111:56‑62.

Coyle JT, Puttfarken P. Oxidative stress, glutamate and neurodegenerative disorders. Science 1993;262:689‑95.

Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 2007;83:84‑92.

Kaizer RR, Correa MC, Spanevello RM, Morsch VM, Mazzanti CM, Gonçalves JF. Acetylcholinesterase activation and enhanced lipid peroxidation after long‑term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 2005;99:1865‑70.

Hargreaves IP, Lane A, Sleiman PM. The coenzyme Q10 status of the brain regions of Parkinson’s disease patients. Neurosci Lett 2008;447:17‑9.

Satoh E, Okada M, Takadera T, Ohyashiki T. Glutathione depletion promotes aluminum‑ mediated cell death of PC12 cells. Biol Pharm Bull 2005;28:941‑6.

Gutteridge JM. Free radicals in disease processes: A compilation of cause and consequence. Free Radic Res Commun 1993;19:141‑58.

Maher P. The effects of stress and aging on glutathione metabolism. Ageing Res Rev 2005;4:288‑314.

Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, et al. Mechanisms of cell death in oxidative stress. Antioxid Redox Signal 2007;9:49‑89.

McCay PB. Vitamin E: Interactions with free radicals and ascorbate. Annu Rev Nutr 1985;5:323‑40.

Kaikkonen J, Nyyssönen K, Tomasi A, Iannone A, Tuomainen TP, Porkkala‑Sarataho E, et al. Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10 and d‑α‑tocopherol in mildly hypercholesterolemic subjects: A randomized placebo‑controlled clinical study. Free Radic Res 2000;33:329‑40.

Feher J, Nemeth E, Nagy V. Gabriella L. The preventive role of coenzyme Q10 and other antioxidants in injuries caused by oxidative stress. Arch Med Sci 2007;3:305‑14.


Refbacks

  • There are currently no refbacks.