EFFECT OF METFORMIN AND SIMVASTATIN IN DIAZEPAM-AND SODIUM NITRITE-INDUCED ANTEROGRADE AMNESIA IN MALE SWISS ALBINO MICE
DOI:
https://doi.org/10.22159/ijpps.2018v10i6.19113Keywords:
Anterograde amnesia, Metformin, Simvastatin, Diazepam, Sodium nitrite, Morris water mazeAbstract
Objective: To study the effect of metformin and simvastatin on diazepam-and sodium nitrite-induced anterograde amnesia in male Swiss albino mice.
Methods: A total of 56 healthy male Swiss albino mice weighing 20–30 g were included in the study Mice were divided into seven groups (n=8) and received a specific dosage of drugs including metformin and simvastatin. Anterograde amnesia was induced by diazepam and sodium nitrite. Morris water maze paradigm was used to study amnesia in which the mice were trained to locate a hidden platform by releasing them into the opaque water for four times a day for four consecutive days. The acquisition of this task was evaluated by measuring escape latency time on all the days of study and by measuring the index of retrieval on day 5 of the study. These observations were compared among the test groups and drug-induced amnesia groups. The time was expressed as mean±standard error of the mean.
Results: Significant reduction in the mean escape latency time (25.25 ± 5.09 s) and index of retrieval (52.38 ± 3.55 s) was observed in groups administered with sodium nitrite and metformin (p<0.001). In groups administered with sodium nitrite and simvastatin, the mean escape latency time and index of retrieval were 47.66 ± 7.69 s and 40.75 ± 4.13 s, respectively (p<0.05)). In addition, metformin completely ameliorated sodium nitrite-induced anterograde amnesia.
Conclusion: Metformin and simvastatin ameliorated sodium nitrite-induced anterograde amnesia pointing toward a possible antioxidant role and can, therefore, be used to potentially inhibit oxidative stress-induced neurodegeneration. However, the pleiotropic roles of metformin and simvastatin are the areas that warrant further investigation before their clinical use.
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References
Gazzaniga M, Ivry R, Mangun G. Cognitive neuroscience: the biology of the mind. New York: W. W. Norton and Company; 2009.
McCance KL, Huether SE, Parkinson C. Pathophysiology: The Biological Basis for Disease in Adults and Children. US: Mosby, Inc.; 2010. p. 106.
Kopelman MD. Disorders of memory. Brain 2002;125:2152-90.
Mohandas E, Rajmohan V, Raghunath B. Neurobiology of Alzheimer's disease. Indian J Psychiatry 2009;51:55-61.
Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008;132:645-60.
Rang HP, Flower RJ, Henderson G. Rang and Dale’s Pharmacology. 7th ed. London: Churchill livingstone, Elsevier; 2007. p. 14.
Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee brothers medical Publishers; 2010. p. 5.
Standaert DG, Roberson ED. Goodman and Gilman’s The Pharmacological Basis of Therapeutics.12th ed. New Delhi: McGraw Hill, Medical; 2011. p. 19.
Cole GM, Morihara T, Lim GP, Yang F, Begum A, Frautschy SA. NSAID and antioxidant prevention of Alzheimer's disease: lessons from in vitro and animal models. Ann N Y Acad Sci 2004;1035:68-84.
Labrousse VF, Nadjar A, Joffre C, Costes L, Aubert A, Gregoire S, et al. Short-term long chain omega3 diet protects from neuroinflammatory processes and memory impairment in aged mice. PLoS One 2012;7:e36861.
Nair G, Van Dyk K, Shah U, Purohit DP, Pinto C, Shah AB, et al. Characterizing cognitive deficits and dementia in an aging urban population in India. Int J Alzheimers Dis 2012:8. http://dx.doi.org/10.1155/2012/673849
Shaji KS, Jotheeswaran AT, Girish N, Bharath S, Dias A, Pattabiraman M, et al. The dementia india report 2010: prevalence, impact, costsandservicesfordementia. New Delhi: Alzheimer’s and Related Disorders Society of India: Available from: 2010. http://www.alzheimer.org.in/assets/dementia.pdf [Last accessed on 10 Mar 2017]
Carlsson CM. Type 2 diabetes mellitus, dyslipidemia, and Alzheimer's disease. J Alzheimers Dis 2010;20:711-22.
Cukierman Yaffe T, Gerstein HC, Williamson JD, Lazar RM, Lovato L, Miller ME, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diab Care 2009;32:221-6.
Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol 2007;64:570-5.
Powers AC, D’Alessio D. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12 ed. Brunton L CB, Knollman B. editor. New York: McGraw-Hill; 1996. p. 19.
Wang J, Gallagher D, DeVito LM, Cancino GI, Tsui D, He L, et al. Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 2012;11:23-35.
Beeri MS, Schmeidler J, Silverman JM, Gandy S, Wysocki M, Hannigan CM, et al. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology 2008;71:750-7.
Launer LJ, Miller ME, Williamson JD, Lazar RM, Gerstein HC, Murray AM, et al. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol 2011;10:969-77.
Andrade C, Radhakrishnan R. The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments. Indian J Psychiatry 2009;51:12-25.
Ghribi O. Potential mechanisms linking cholesterol to Alzheimer's disease-like pathology in rabbit brain, hippocampal organotypic slices, and skeletal muscle. J Alzheimers Dis 2008;15:673-84.
Barone E, Di Domenico F, Butterfield DA. Statins more than cholesterol-lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets. Biochem Pharmacol 2014;88:605-16.
Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, et al. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology 2007;69:878-85.
Boimel M, Grigoriadis N, Lourbopoulos A, Touloumi O, Rosenmann D, Abramsky O, et al. Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy. J Neuropathol Exp Neurol 2009;68:314-25.
Tandon V, Bano G, Khajuria V, Parihar A, Gupta S. Pleiotropic effects of statins. Indian J Pharmacol 2005;37:77.
Dhingra D, Kumar V. Memory-enhancing activity of palmatine in mice using elevated plus maze and morris water maze. Adv Pharmacol Sci 2012:1-7. http://dx.doi.org/10.1155/2012/ 357368
Myhrer T. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res Brain Res Rev 2003;41:268-87.
Mihic SJ, Harris RA. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Brunton L CB, Knollman B. editor. New Delhi: McGraw Hill Medical; 2011. p. 23.
Bromley Brits K, Deng Y, Song W. Morris water maze test for learning and memory deficits in Alzheimer's disease model mice. J Vis Exp 2011;53. Doi:10.3791/2920.
Mihic SJ, Harris RA. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed ed. Brunton LCB, Knollman B. editor. New Delhi: McGraw Hill Medical; 2011. p. 24.
Savic MM, Obradovic DI, Ugrešic ND, Bokonjic DR. Memory effects of benzodiazepines: Memory stages and types versus binding-site subtypes. Neural Plast 2005;12:289-98.
Porsolt RD, Lenegre A, Avril I, Doumont G. Antagonism by exifone, a new cognitive enhancing agent, of the amnesias induced by four benzodiazepines in mice. Psychopharmacology (Berl) 1988;95:291-7.
Hlinak Z, Krejci I, Hondlik J, Yamamoto A. Behavioral consequences of sodium nitrite hypoxia in male rats: Amelioration with alaptide treatment. Methods Find Exp Clin Pharmacol 1990;12:385-93.
Schindler U, Rush DK, Fielding S. Nootropic drugs: animal models for studying effects on cognition. Drug Dev Res 1984;4:567-76.
Bhattacharya SK. Nootropic effect of BR-16A (Mentat), a psychotropic herbal formulation, on cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverishment and hypoxia in rats. Indian J Exp Biol 1994;32:31-6.
Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47-60.
Maei HR, Zaslavsky K, Teixeira CM, Frankland PW. What is the most sensitive measure of water maze probe test performance? Front Integr Neurosci 2009;3:4.
Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs 2004;18:37-48.
Maric A. Metformin-more than 'gold standard' in the treatment of type 2 diabetes mellitus. Diabetologia Croatica 2010;39:9.
Zhu X, Lee HG, Perry G, Smith MA. Alzheimer disease, the two-hit hypothesis: an update. Biochim Biophys Acta 2007;1772:494-502.
Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-kappaB signalling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl) 2011;89:667-76.
Bersot TP. Goodman and gilman’s the pharmacological basis of therapeutics. 12 ed. Brunton LCB, Knollman B. editor. New Delhi: McGraw Hill Medical; 2011. p. 877-908.
Nakagami H, Jensen KS, Liao JK. A novel pleiotropic effect of statins: prevention of cardiac hypertrophy by cholesterol-independent mechanisms. Ann Med 2003;35:398-403.
Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 2011; 77:556-63.
Albert MA, Danielson E, Rifai N, Ridker PM, Investigators P. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001;286:64-70.
Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005;64:1152-6.
Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001;60:759-67.
Oka M, Fagan KA, Jones PL, McMurtry IF. Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br J Pharmacol 2008;155:444-54.
Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 2000;1:120-9.
Hadidchi MS, Shenoy UV, Thomas JM, Vupputuri RS. Study of awareness among healthcare providers for the need to periodically screen renal functions in diabetic patients receiving metformin. Int J Curr Pharm Res 2015;7:51-3.