Abstract
Potential use of various nootropic drugs have been a burning area of research on account of various physical and chemical insult in brain under different toxicological conditions. One of the nootropic drug Centrophenoxine, also known as an anti-aging drug has been exploited in the present experiment under aluminium toxic conditions. Aluminium was administered by oral gavage at a dose level of 100 mg/Kg b.wt/day for a period of six weeks. To elucidate the region specific response, study was carried out in two different regions of brain namely Cerebrum and Cerebellum. Following aluminium exposure, a significant decrease in the activities of enzymes namely Hexokinase, Lactate dehydrogenase, Succinate dehydrogenase, Mg2+ dependent ATPase was observed in both the regions. Moreover, the activity of acetylcholinesterase was also reported to be significantly decreased. Post-treatment with Centrophenoxine was able to restore the altered enzyme activities and the effect was observed in both the regions of brain although the activity of lactate dehydrogenase and acetylcholinesterase did not register significant increase in the cerebellum region. Further, Centrophenoxine was able to improve the altered short-term memory and cognitive performance resulted from aluminium exposure. From the present study, it can be concluded that Centrophenoxine has a potential and can be exploited in other toxicological conditions also.
Similar content being viewed by others
References
Flaten TP: Aluminum is a risk factor in Alzheimer disease, with emphasis on drinking water. Brain Research Bull. 55(2): 152–167, 2001
Campbell A, Prasad KN, Bondy SC: Aluminum-induced oxidative events in cell lines: Glioma are more responsive than neuroblastoma. Free Radic Biol Med 26: 1166–1171, 1999
DeStasio G, Marcanti D, Ciotti MT, Dunham D, Drounay TC, Tonner BP, Perfetti P, Margaritondo G: Aluminum in rat cerebellar neural cultures. Neuroreport 5: 1173–1178, 1994
Favarato M, Zatta PF, Perazzolo M, Fontana l, Nicolini M: Al (III) influences the permeability of blood brain barrier to [14C] sucrose in rats. Brain Res 569: 330–335, 1992
Banks WA, Kastin AJ, Zatta P: The blood brain aluminium toxicity and Alzheimer's disease. In: P. Zatta and M. Nicolini (eds). Non neuronal Cells in Alzheimer's disease. World Scientific, Singapore, 1995, pp. 1–12.
McLanchan DR, Vaan Berkum MFA: Aluminium: A role in degenerative brain disease associated with neurofibrillary degeneration. Progress in Brain Research 70: 339–410, 1986
Edwardson JA, Moore PB, Ferrier IN, Lilley JS, Newton GWA, Barker J, Templar J, Day JP: Effect of silicon on gastrointestinal absorption of aluminium. Lancet 342(7): 211–212, 1993
Ravi SM, Prabhu BM, Raju TR, Bindu PN: Long term effects of post natal aluminium exposure on acetylcholinesterase activity and biogenic amine neurotransmitters in rat brain. Indian J Physiol Pharmacol 44 (4): 473–478, 2000
Cho S, Joshi JG: Effect of long-term feeding of aluminium chloride on hexokinase and glucose-6-phosphate dehydrogenase in the brain. Toxicology 48: 61–89, 1988
Excley C, Price NC, Birchall JD: Aluminium inhibition of hexokinase activity in vitro: A study in biological availability. J Inorg Biochem 54: 297–304, 1994
Xu ZX, Fox L, Melethil S, Winberg L, Badr M: Mechanism of aluminium induced inhibition of hepatic glycolysis: inactivation of phosphofructokinase. J Pharm Exp Ther 254: 301–305, 1990
Zs-Nagy I: A survey of the available data on a new nootropic drug, BCE-001. Ann NY Acad Sci 717: 102–114, 1994
Zs-Nagy I, Pieri C, Giuli C, Del Moro M: Effects of centrophenoxine on the monovalent electrolyte contents of the large brain cortical cells of old rats. Gerontology 25: 94–102, 1979
Zs-Nagy I, Semsei I: Centrophenoxine increases the rates of total and mRNA synthesis in the brain cortex of old rats: An explanation of its action in terms of the membrane hypothesis of aging. Exp Gerontol 19(3): 171–8, 1984
Mangal PC, Gulati N: Trace elements in animal feed and element tissues: A correlation study by neutron activation method. Ind J Exp Biol 19: 441–444, 1981
Ellman GL, Courtney KD, Andres VJ, FeatherstoneAL: A new and rapid colorimetric determination of acetylcholiesterase activity. Biochem pharmacol 7: 88–95, 1961
Crane RK, Sols A: Animal tissue hexokinase. In: S.P. Colowick and N.O. Kaplan (eds). Methods in enzymology, Vol. I. New York, Academic Press, 1965, pp 277–278
Fiske SH, Subbarow Y: Colorimetric determination of phosphorous. J Biol Chem 66: 375, 1925
King J: Colorimetric estimation of lactate dehydrogenase. J Med Lab Tech 16: 265, 1959
Kun E, Abood LG: Colorimetric estimation of succinate dehydrogenase by triphenyl tetrzolium chloride. Science 109: 144, 1949
Kielley NW: Mitochondrial ATPase, In: S.P. Colowick and N.O. Kaplan (eds). Methods in enzymology, Vol. 2 Academic Press, New York 1965, pp 583–585
Lowry OH, Rosebrough NJ, Farr AL, Ranell, RJ: Protein measurements with the Follin's phenol reagent. J Biol Chem 193: 265, 1951
Edwardson JA, Ferrier IN, McArthur FK, McKeith IG, McLaughlin I, Morris CM, Mountfort SA, Oakley AE, Taylor GA, Ward MK, Candy JM: Alzheimer's disease and the aluminium hypothesis. In: M. Nicoloni PF, Zatta B, Cortain (eds). Aluminium in chemistry, Biology and Medicine, Raven Press, New York, USA, 1991, pp 84–96
Neff NH, Garrison JK, Fuendes J, Seabord JB, Wyatt RJ: Trace amines and the monoamineoxidase. In: E. Usdina, M. Sandler (eds). Trace amines and the brain. New York, Marcel Dekker, 1976, pp 41–42
Trapp GA: Studies of aluminium interaction with enzymes and proteins-the inhibition of hexokinase. Neurotoxicology 1: 89–100, 1980
Lai JCK, John PB: Inhibition of brain glycolysis by aluminium. J Neurochem 42: 438–446, 1984
Martin RB: The chemistry of aluminium as related to biology and medicine. Clin Chem 32: 1797–1806, 1986
Lehninger AL: The tricarboxylic acid cycle. In: Lehninger (eds). Biochemistry, Kalyani Publishers, New Delhi, India, 1993, pp 459
Chinoy NJ, Memom MR: Beneficial effect of some vitamins and calcium n fluoride and aluminium toxicity on gastroenemius muscle and liver of male mice. Fluoride 34 (1): 21–33, 2001
Guest J: The effects of aluminium on sodium-potassium-activated adenosine triphosphatase activity and choline uptake in rat brain synaptosomes. Biochem Pharmacol 29: 141–145, 1980
Holtzman D, Hsu JS, Desautel M: Absence of effects of lead feedings and growth retardation on mitochondrial and cytochromes in the developing brain. Toxicol Appl Pharmacol 58: 48–56, 1981
Schwartz BS, Stewart WF, Bolla KI, Simon PD: Past adult exposure is associated with longitudinal decline in cognitive function. Neurology 55 (8): 1144–1150, 2000
Connor DJ, Harrel LE. Jopes RS: Reversal of an aluminium induced behavior defiect by administration of deferoxamine. Behave Neurosci 103: 779–83, 1989
Marcer D, Hopkins S: The differential effects of meclofenoxate on memory loss in the elderly. Age and Aging 6: 123–131, 1977
Sharma D, Singh R: Response of age related interneuronal cytomorphological impairments to the Centrophenoxine in the pyramidal neurons of lamina pyramidalis (layer 5) in cerebral cortex in aged rats. Proc Nat Acad Sci India 61 (B): 1, 1991
Destrem H: Essai clinique de la Centrophenoxine en geriatrie (52, cas), Presse Med. 69: 1999–2001, 1961
Nandy K: Lipofuscinogenesis in mice early treated with centrophenoxine. Mech Age Dev 8: 131–138, 1978
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nehru, B., Bhalla, P. & Garg, A. Evidence for centrophenoxine as a protective drug in aluminium induced behavioral and biochemical alteration in rat brain. Mol Cell Biochem 290, 33–42 (2006). https://doi.org/10.1007/s11010-006-9125-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-006-9125-7