Comparative Study of the Effects of Metformin and Garlic Extract on Hippocampal Na<sup>+</sup>/K<sup>+</sup> ATPase, Ca<sup>2+</sup> ATPase and Glutamine Synthetase Activities in Type II Diabetic Wistar Rat — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Comparative Study of the Effects of Metformin and Garlic Extract on Hippocampal Na<sup>+</sup>/K<sup>+</sup> ATPase, Ca<sup>2+</sup> ATPase and Glutamine Synthetase Activities in Type II Diabetic Wistar Rat
Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
,
Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
,
Department of Anatomy, St. Francis University College of Health and Applied Sciences, Ifakara, Tanzania
,
Department of Anatomy, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
,
Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
,
Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
,
Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
,
Department of Physiology, Faculty of Biomedical Sciences, St. Augustine International University, Kampala, Uganda
1 Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
2 Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
3 Department of Anatomy, St. Francis University College of Health and Applied Sciences, Ifakara, Tanzania
4 Department of Anatomy, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
5 Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
6 Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
7 Department of Physiology, Faculty of Biomedical Sciences, Kampala International University, Ishaka, Uganda
8 Department of Physiology, Faculty of Biomedical Sciences, St. Augustine International University, Kampala, Uganda
Diabetes mellitus has not ceased to be on rise in spite of the continuous research on its management. Brain dysfunction associated with Diabetes mellitus especially Type II has been the great concern. The aim of this study was to investigate the effect of insulin sensitizing drug metformin and ethanolic extract of garlic on membrane bound enzymes Na + /K + ATPase, Ca 2+ ATPase and glutamate-glutamine cycle enzyme, Glutamine Synthetase activities in the hippocampus of streptozotocin-Nicotinamide induced Type II Diabetic rats. Twenty four male wistar rats weighted 120 - 150 g were used and divided into four groups with six rats in each group. Group A was non-diabetic (Control) and Groups B, C and D were diabetic. Group B received no treatment (DNT) while Groups C and D were treated with 1000 mg/kg of ethanolic garlic extract (EGE) and 50 mg/kg of metformin (MET) respectively orally for three weeks. All the groups were fed on standard rat chow with water ad libitum. Blood glucose was monitored weekly. Animals were sacrificed and the brains were removed and hippocampi were carefully excised and homogenate were obtained. Homogenate was analyzed for Na + /K + ATPase, Ca 2+ ATPase and Glutamine Synthetase (GS) activities. MET and EGE significantly reduced the blood glucose levels. There was a significant increase in the activities of hippocampal Na + /K + ATPase, Ca 2+ ATPase and GS in MET and EGE when compared to DNT. The results suggest that both MET and EGE increase the activities of hippocampal Na + /K + ATPase, Ca 2+ ATPase and GS which were reduced by diabetes mellitus, thus garlic and metformin administration exhibiting neuroprotective effect during hippocampal-related disorders associated with diabetes mellitus.
Sacai, H., Sasaki-Hamada, S., Sugiyama, A., Saitoh, A., Mori, K., Yamada, M. and Oka, J. (2014) The Impairment in Spatial Learning and Hippocampal LTD Induced through the PKA Pathway in Juvenile-Onset Diabetes Rats Are Rescued by Modulating NMDA Receptor Function. Neuroscience Research, 81-82, 55-63. https://doi.org/10.1016/j.neures.2014.02.002
Stevens, M.J., Dananberg, J., Feldman, E.L., Lattimer, S.A., Kamijo, M., Thomas, T.P., Shindo, H., Sima, A.A. and Greene, D.A. (1994) The Linked Roles of Nitric Oxide, Aldose Reductase and (Na+- K+)- ATPase in the Slowing of Nerve Conduction in the Streptozotocin Diabetic Rat. Journal of Clinical Investigation, 94, 853-859. https://doi.org/10.1172/JCI117406
Vague, P., Coste, T.C., Jannot, M.F., Raccah, D. and Tsimaratos, M. (2004) C-Peptide, Na+, K+-ATPase, and Diabetes. Experimental Diabesity Research, 5, 37-50. https://doi.org/10.1080/15438600490424514
Welsh, B. and Wecker, L. (1991) Effects of Streptozotocin-Induced Diabetes on Acetylcholine Metabolism in Rat Brain. Neurochemical Research, 16, 453-460. https://doi.org/10.1007/BF00965566
Aubier, M. and Viires, N. (1998) Calcium ATPase and Respiratory Muscle Function. The European Respiratory Journal, 11, 758-766.
Kamboj, S.S., Chopra, K. and Sandhir, R. (2009) Hyperglycemia-Induced Alterations in Synaptosomal Membrane Fluidity and Activity of Membrane Bound Enzymes: Beneficial Effect of N-Acetylcysteine Supplementation. Neuroscience, 162, 349-358. https://doi.org/10.1016/j.neuroscience.2009.05.002
Khakpai, F., Nasehi, M., Haeri-Rohani, A., Eidi, A. and Zarrindast, M.R. (2012) Scopolamine Induced Memory Impairment Possible Involvement of NMDA Receptor Mechanisms of Dorsal Hippocampus and/or Septum. Behavioural Brain Research, 231, 1-10. https://doi.org/10.1016/j.bbr.2012.02.049
Szatkowski, M. and Attwell, D. (1994) Triggering and Execution of Neuronal Death in Brain Ischaemia: Two Phases of Glutamate Release by Different Mechanisms. Trends in Neurosciences, 17, 359-365. https://doi.org/10.1016/0166-2236(94)90040-X
Chen, J. and Herrup, K. (2012) Glutamine Acts as a Neuroprotectant against DNA Damage, Beta-Amyloid and H2O2-Induced Stress. PLoS ONE, 7, e33177. https://doi.org/10.1371/journal.pone.0033177
Zheng, Y., Yang, Y., Dong, B., Zheng, H., Lin, X., Du, Y., Li, X., Zhao, L. and Gao, H. (2016) Metabonomic Profile Delineate Potential Role of Glutamate-Glutamine Cycle in db/db Mice with Diabetes-Associated Cognitive Decline. Molecular Brain, 18, 9-40. https://doi.org/10.1186/s13041-016-0223-5
/K<
sup>
+<
/sup>
ATPase
Pintana, H., Apaijai, N., Pratchayasakul, W., Chattipakorn, N. and Chattipakorn, S.C. (2012) Effects of Metformin on Learning and Memory Behaviors and Brain Mitochondrial Functions in High Fat Diet Induced Insulin Resistant Rats. Life Sciences, 91, 409-414. https://doi.org/10.1016/j.lfs.2012.08.017
Yuan, X., Chen, Y.B., Gan, D.N., Cheng, Y.F. and Xu, J.P. (2014) Metformin Improves Learning and Memory of Rats Induced by High-Fat Diet. Military Medical Sciences, 38, 17-21.
Zhang, W.H., Liu, Z., Shi, F.G. and Chen, Z.M. (2012). Huanglianwendan Tang in Mice with Type 2 Diabetes and the Impact on the Learning and Memory and the Form of Hippocampal Nerve Cells. Lishizhen Medicine and Materia Medica Research, 23, 948-949.
Oliveira, W.H., Nunes, A.K., Franca, M.E., Santos, L.A., Los, D.B., Rocha, S.W., Barbosa, K.P., Rodrigues, G.B. and Peixoto, C.A. (2016) Effect of Metformin on Inflammation and Short-Term Memory in Streptozotocin-Induced Diabetic Mice. Brain Research, 1644, 149-160. https://doi.org/10.1016/j.brainres.2016.05.013
Mo, W. and Qian, G.F. (2014) Metformin for High Fat Diet Induced Insulin Resistance the Effect of Space Cognition, Learning and Memory and Cerebral Energy Metabolism. Chinese Journal of Gerontology, 34, 2813-2815.
Asadbegi, M., Yaghmaei, P., Salehi, I., Ebrahim-Habibi, A. and Komaki, A. (2016) Neuroprotective Effects of Metformin against a β-Mediated Inhibition of Long-Term Potentiation in Rats Fed a High-Fat Diaet. Brain Research Bulletin, 121, 178-185. https://doi.org/10.1016/j.brainresbull.2016.02.005
Anwar, M. and Meki, A. (2003) Oxidative Stress in Streptozotocin-Induced Diabetic Rats: Effects of Garlic Oil and Melatonin. Comparative Biochemistry and Physiology Part A, 135, 539-547. https://doi.org/10.1016/S1095-6433(03)00114-4
Thomson, M., Al-Amin, Z.M., Al-Qattan, K.K., Shaban, L.H. and Ali, M. (2006) Anti-Diabetic and Hypolipidaemic Properties of Garlic (Allium sativum) in Streptozotocin Induced Diabetic Rats. International Journal of Diabetes and Metabolism, 15, 108-115.
Drobiova, H., Thomson, M., Al-Qattan, K., Peltonen-Shalaby, R., Al-Amin, Z. and Ali, M. (2011) Garlic Increases Antioxidant Levels in Diabetic and Hypertensive Rats Determined by a Modified Peroxidase Method. Evidence-Based Complementary and Alternative Medicine, 2011, Article ID: 703049.
Liu, C.T., Hse, H., Lii, C.K., Chen, P.S. and Sheen, L.Y. (2005) Effects of Garlic Oil and Diallyl Trisulfide on Glycemic Control in Diabetic Rats. European Journal of Pharmacology, 516, 165-173. https://doi.org/10.1016/j.ejphar.2005.04.031
Shiju, T.M., Rajesh, N.G. and Viswanathan, P. (2013) Renoprotective Effect of Aged Garlic Extract in Streptozotocin-Induced Diabetic Rats. Indian Journal of Pharmacology, 45, 18-23.
Sarkaki, A., Valipour, S.C., Farbood, Y., Mohammad, S., Mansouri, T., Naghizadeh, B. and Basirian, E. (2013) Effects of Fresh, Aged and Cooked Garlic Extracts on Short- and Long-Term Memory in Diabetic Rats. Avicenna Journal of Phytomedicine, 3, 45-55.
Safiriyu, A.A., Semuyaba, I., RemónFigueredo, N., Etibor, T.A. and Ajibola, M.I. (2017) Garlic Extract (Allium sativum) Enhances Spatial Working Memory in Wistar Rats: Involvement of Hippocampal Na+/K+ ATPase and Ca2+ ATPase Activities. Journal of Behavioral and Brain Science, 7, 31-40. https://doi.org/10.4236/jbbs.2017.72004
Semuyaba, I., Safiriyu, A.A., Tiyo, E.A. and Remón-Figueredo, N. (2017) Memory Improvement Effect of Ethanol Garlic (A. sativum) Extract in Streptozotocin-Nicotinamide Induced Diabetic Wistar Rats Is Mediated through Increasing of Hippocampal Sodium-Potassium ATPase, Glutamine Synthetase, and Calcium ATPase Activities. Evidence-Based Complementary and Alternative Medicine, 3, 1-7. https://doi.org/10.1155/2017/3720380
Homayounfar, H., BaluchnejadMojarad, T., Roghani, M., Hosseini, M. and Kamalinejad, M. (2003) Effect of Aqueous Garlic (Allium sativum L.) Extract on Acetylcholine and Isosorbide-Induced Relaxation of Isolated Aorta in Rat. Iranian Biomedical Journal, 7, 23-27.
Marudamuthu, A.S. and Leelavinothan, P. (2008) Emerging Targets Effect of Pterostilbene on Lipids and Lipid Profiles in Streptozotocin-Nicotinamide Induced Type 2. Journal of Applied Biomedicine, 6, 31-37.
Tirri, R., Lagrspetz, K.Y.H. and Kohomen, J. (1973) Temperature Dependence of the ATPase Activity in Brain Homogenates during the Postnatal Development of Rat. Comparative Biochemistry and Physiology, 44, 473-480.
Fiske, C.H. and Subba Row, Y. (1925) The Colorimetric Determination of Phosphates. The Journal of Biological Chemistry, 66, 375-400.
Desaiah, D. and Ho, I.K. (1979) Effect of Acute and Continuous Morphine Administration on Catecholamine-Sensitive Adenosine Triphosphatase in Mouse Brain. Journal of Pharmacology and Experimental Therapeutics, 208, 80-85.
Rowe, W.B., Ronzio, R.A., Wellner, V.P. and Meister, A. (1970) Glutamine Synthetase (Sheep Brain) Methods. Enzymology, 17, 900-910. https://doi.org/10.1016/0076-6879(71)17304-1
Lotfi, N., Hami, J., Hosseini, M., Haghir, D. and Haghir, H. (2016) Diabetes during Pregnancy Enhanced Neuronal Death in the Hippocampus of Rat Offspring. International Journal of Developmental Neuroscience, 51, 28-35. https://doi.org/10.1016/j.ijdevneu.2016.04.009
Sadeghi, A., Ebrahimzadeh Bideskan, A.R., Alipour, F., Fazel, A.R. and Haghir, A. (2013) The Effect of Ascorbic Acid and Garlic Administration on Lead-Induced Neural Damage in Rat Offspring’s Hippocampus. Iranian Journal of Basic Medical Sciences, 16, 157-164.
Wang, J., Gallagher, D., DeVito, L.M., Cancino, G.I., Tsui, D., He, L., Keller, G.M., Frankland, P.W., Kaplan, D.R. and Miller, F.D. (2012) Metformin Activates an Atypical PKC-CBP Pathway to Promote Neurogenesis and Enhance Spatial Memory Formation. Cell Stem Cell, 11, 23-35. https://doi.org/10.1016/j.stem.2012.03.016
Lennox, R., Porter, D.W., Flatt, P.R., Holscher, C., Irwin, N. and Gault, V.A. (2014) Comparison of the Independent and Combined Effects of Sub-Chronic Therapy with Metformin and a Stable GLP-1 Receptor Agonist on Cognitive Function, Hippocampal Synaptic Plasticity and Metabolic Control in High-Fat Fed Mice. Neuropharmacology, 86, 22-30. https://doi.org/10.1016/j.neuropharm.2014.06.026