Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation and Characterization of CurNP and ZnONP Nanoparticles
2.2. Experimental Animals
2.3. Type 2 Diabetes and Neurodegeneration Rat Model
2.4. Morris Water Maze Test (MWM)
2.5. Sample Preparation and Biochemical Evaluations
2.6. Measurement of Hippocampal Oxidant and Antioxidant Biomarkers
2.7. Quantification of Serum Adipokines Levels and Hippocampal IL-6 and TNF-α
2.8. Quantification of Acetylcholine Esterase Activity (AChE), IDE, and Aβ-42 Concentrations
2.9. Real-Time Polymerase Chain Reaction (RT-PCR)
2.10. Western Blotting
2.11. Histological Analysis
2.12. Statistical Analysis
3. Results
3.1. Characterization of ZnONP and CurNP
3.2. Effects of CurNP and ZnONP on Memory Deficits in T2DM-Induced Rat Models
3.3. Blood Glucose, Insulin, and AGEs Levels
3.4. Hippocampal Concentrations of Oxidant and Antioxidant Biomarkers
3.5. Alteration of Concentrations of Serum Adipokines and Hippocampal Inflammatory Mediators
3.6. Regulation of AChE Activity, IDE Level, and Aβ-42 Clearance in the Hippocampus of Rats
3.7. Gene Expression Profile of APP, BACE-1, BDNF, and ADAM-10 in the Hippocampus of Rats
3.8. Effect of CurNP and ZnONP on an Apoptotic Pathway in the Hippocampus and Cortex of Rats
3.9. p38-MAPK Signaling Cascade and Tau Protein in the Hippocampus of Rats
3.10. Histopathological Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Verbeek, M.M.; Eikelenboom, P.; de Waal, R.M. Differences between the pathogenesis of senile plaques and congophilic angiopathy in Alzheimer disease. J. Neuropathol. Exp. Neurol. 1997, 56, 751–761. [Google Scholar] [CrossRef]
- Rao, C.V.; Asch, A.S.; Carr, D.J.; Yamada, H.Y. Amyloid-beta accumulation cycle as a prevention and/or therapy target for Alzheimer’s disease. Aging Cell 2020, 19, e13109. [Google Scholar] [CrossRef]
- Marcus, J.N.; Schachter, J. Targeting post-translational modifications on tau as a therapeutic strategy for Alzheimer’s disease. J. Neurogenet. 2011, 25, 127–133. [Google Scholar] [CrossRef] [PubMed]
- Rönnemaa, E.; Zethelius, B.; Sundelöf, J.; Sundström, J.; Degerman-Gunnarsson, M.; Berne, C.; Lannfelt, L.; Kilander, L. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology 2008, 71, 1065–1071. [Google Scholar] [CrossRef]
- Carvalheira, J.B.; Ribeiro, E.B.; Araújo, E.P.; Guimarães, R.B.; Telles, M.M.; Torsoni, M.; Gontijo, J.A.R.; Velloso, L.A.; Saad, M.J.A. Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats. Diabetologia 2003, 46, 1629–1640. [Google Scholar] [CrossRef] [Green Version]
- Soumya, D.; Srilatha, B. Late-stage complications of diabetes and insulin resistance. J. Diabetes Metab. 2011, 2, 1672. [Google Scholar]
- Weinstein, G.; Maillard, P.; Himali, J.J.; Beiser, A.S.; Au, R.; Wolf, P.A.; Seshadri, S.; DeCarli, C. Glucose indices are associated with cognitive and structural brain measures in young adults. Neurology 2015, 84, 2329–2337. [Google Scholar] [CrossRef] [Green Version]
- Lu, M.J.; Zhu, Y.; Sun, J.; Yang, X.R. Microglia mediates inflammation injury in mouse models of Parkinson’s disease. Zhongguo Zuzhi Gongcheng Yanjiu 2011, 15, 1945–1948. [Google Scholar]
- Hein, A.M.; O’Banion, M.K. Neuroinflammation and cognitive dysfunction in chronic disease and aging. J. Neuroimmune Pharmacol. 2012, 7, 3–6. [Google Scholar] [CrossRef] [PubMed]
- Park, J.C.; Han, S.H.; Mook-Jung, I. Peripheral inflammatory biomarkers in Alzheimer’s disease: A brief review. BMB Rep. 2020, 53, 10. [Google Scholar] [CrossRef] [PubMed]
- e Silva, N.M.L.; Gonçalves, R.A.; Pascoal, T.A.; Lima-Filho, R.A.; Resende, E.D.P.F.; Vieira, E.L.; Teixeira, A.L.; de Souza, L.C.; Peny, J.A.; Fortuna, J.T.; et al. Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. Transl. Psychiatry 2021, 11, 1–15. [Google Scholar]
- Pizza, V.; Agresta, A.; D’Acunto, C.W.; Festa, M.; Capasso, A. Neuroinflammation and ageing: Current theories and an overview of the data. Rev. Recent Clin. Trials 2011, 6, 189–203. [Google Scholar] [CrossRef]
- Arthur, J.S.; Ley, S.C. Mitogen-activated protein kinases in innate immunity. Nat. Rev. Immunol. 2013, 13, 679–692. [Google Scholar] [CrossRef]
- Albert-Gascó, H.; Ros-Bernal, F.; Castillo-Gómez, E.; Olucha-Bordonau, F.E. MAP/ERK signaling in developing cognitive and emotional function and its effect on pathological and neurodegenerative processes. Int. J. Mol. Sci. 2020, 21, 4471. [Google Scholar] [CrossRef] [PubMed]
- Jayaraj, R.L.; Azimullah, S.; Beiram, R.; Jalal, F.Y.; Rosenberg, G.A. Neuroinflammation: Friend and foe for ischemic stroke. J. Neuroinflamm. 2019, 16, 142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xing, L.; Larsen, R.S.; Bjorklund, G.R.; Li, X.; Wu, Y.; Philpot, B.D.; Snider, W.D.; Newbern, J.M. Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex. eLife 2016, 5, e11123. [Google Scholar] [CrossRef] [Green Version]
- Faucher, P.; Mons, N.; Micheau, J.; Louis, C.; Beracochea, D.J. Hippocampal injections of oligomeric amyloid β-peptide (1-42) induce selective working memory deficits and longlasting alterations of ERK signaling pathway. Front. Aging Neurosci. 2015, 7, 245. [Google Scholar] [PubMed] [Green Version]
- Lenzen, S. The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia 2008, 51, 216–226. [Google Scholar] [CrossRef] [Green Version]
- Szkudelski, T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res. 2001, 50, 537–546. [Google Scholar]
- Yang, F.; Lim, G.P.; Begum, A.N.; Ubeda, O.J.; Simmons, M.R.; Ambegaokar, S.S.; Chen, P.P.; Kayed, R.; Glabe, C.G.; Frautschy, S.A.; et al. Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem. 2005, 280, 5892–5901. [Google Scholar] [CrossRef] [Green Version]
- Khan, A.; Jahan, S.; Imtiyaz, Z.; Alshahrani, S.; Antar Makeen, H.; Mohammed Alshehri, B.; Kumar, A.; Arafah, A.; Rehman, M.U. Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals. Biomedicines 2020, 8, 284. [Google Scholar] [CrossRef]
- Agrawal, R.; Mishra, B.; Tyagi, E.; Nath, C.; Shukla, R. Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat. Pharm. Res. 2010, 61, 247–252. [Google Scholar] [CrossRef] [PubMed]
- ELBini-Dhouib, I.; Doghri, R.; Ellefi, A.; Degrach, I.; Srairi-Abid, N.; Gati, A. Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease. Molecules 2021, 26, 3011. [Google Scholar] [CrossRef] [PubMed]
- Caesar, I.; Jonson, M.; Nilsson, K.P.R.; Thor, S.; Hammarström, P. Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila. PLoS ONE 2012, 7, e31424. [Google Scholar] [CrossRef] [Green Version]
- Ege, D. Action Mechanisms of Curcumin in Alzheimer’s Disease and Its Brain Targeted Delivery. Materials 2021, 14, 3332. [Google Scholar] [CrossRef] [PubMed]
- Burgos-Morón, E.; Calderón-Montaño, J.M.; Salvador, J.; Robles, A.; López-Lázaro, M. The dark side of curcumin Estefanía. Int. J. Cancer 2010, 126, 1771–1775. [Google Scholar]
- Basnet, P.; Skalko-Basnet, N. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules 2011, 16, 4567–4598. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Modasiya, M.; Patel, V. Studies on solubility of curcumin. Int. J. Pharm. Life Sci. 2012, 3, 1490–1497. [Google Scholar]
- Mohanty, C.; Sahoo, S.K. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials 2010, 31, 6597–6611. [Google Scholar] [CrossRef]
- Mishra, P.K.; Mishra, H.; Ekielski, A.; Talegaonkar, S.; Vaidya, B. Zinc oxide nanoparticles: A promising nanomaterial for biomedical applications. Drug Discov. 2017, 22, 1825–1834. [Google Scholar] [CrossRef]
- Smijs, T.G.; Pavel, S. Titanium dioxide and zinc oxide nanoparticles in sunscreens: Focus on their safety and effectiveness. Nanotechnol. Sci. Appl. 2011, 4, 95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ruszkiewicz, J.A.; Pinkas, A.; Ferrer, B.; Peres, T.V.; Tsatsakis, A.; Aschner, A. Neurotoxic effect of active ingredients in sunscreen products, a contemporary review. Toxicol. Rep. 2017, 4, 245–259. [Google Scholar] [CrossRef]
- Xiong, H.M. ZnO nanoparticles applied to bioimaging and drug delivery. Adv. Mater. 2013, 25, 5329–5335. [Google Scholar] [CrossRef] [PubMed]
- Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951, 193, 265–275. [Google Scholar] [CrossRef]
- Matthews, D.R.; Hosker, J.P.; Rudenski, A.S.; Naylor, B.A.; Treacher, D.F.; Turner, R.C. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1981, 28, 412–419. [Google Scholar] [CrossRef] [Green Version]
- Tappel, A.; Zalkin, H. Lipid peroxidation in isolated mitochondria. Arch. Biochem. Biophys. 1959, 80, 326–332. [Google Scholar] [CrossRef]
- Montgomery, H.; Dymock, J. Colorimetric determination of nitric oxide. Analyst 1961, 86, 414–417. [Google Scholar]
- Jollow, D.; Mitchell, J.; Zampaglione, N.; Gillette, J.R. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 1974, 11, 151–169. [Google Scholar] [CrossRef] [PubMed]
- Habig, W.; Pabst, M.; Jakoby, W. Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 1974, 249, 7130–7139. [Google Scholar] [CrossRef]
- Marklund, S.; Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 1974, 47, 469–474. [Google Scholar] [CrossRef] [PubMed]
- Aebi, H. Catalase in vitro. Methods Enzymol. 1984, 105, 121–126. [Google Scholar]
- Paglia, D.; Valentine, W. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 1967, 70, 158–169. [Google Scholar]
- Ellman, G.L.; Courtney, K.D.; Andres, V.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88–95. [Google Scholar] [CrossRef]
- Livak, K.; Schmittgen, T. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001, 25, 402–408. [Google Scholar] [CrossRef] [PubMed]
- Burnette, W. Western blotting: Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal. Biochem. 1981, 112, 195–203. [Google Scholar] [CrossRef]
- Ramachandran, S.; Asokkumar, K.; Uma Maheswari, M.; Ravi, T.; Sivashanmugam, A.; Saravanan, S.; Rajasekaran, A.; Dharman, J. Investigation of antidiabetic, antihyperlipidemic, and in vivo antioxidant properties of Sphaeranthus indicus Linn. in type 1 diabetic rats: An identification of possible biomarkers. Evid. Based Complement. Altern. Med. 2011, 2011, 571721. [Google Scholar] [CrossRef] [Green Version]
- Balbaa, M.; Abdulmalek, S.A.; Khalil, S. Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs. PLoS ONE 2017, 12, e0172429. [Google Scholar] [CrossRef] [Green Version]
- Salkovic-Petrisic, M.; Hoyer, S. Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: An experimental approach. Neuropsychiatr. Disord. Integr. Approach 2007, 72, 217–233. [Google Scholar]
- Shehzad, A.; Ha, T.; Subhan, F.; Lee, Y.S. New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases. Eur. J. Nutr. 2011, 50, 151–161. [Google Scholar] [CrossRef]
- Nazarizadeh, A.; Asri-Rezaie, S. Comparative study of antidiabetic activity and oxidative stress induced by zinc oxide nanoparticles and zinc sulfate in diabetic rats. AAPS PharmSciTech 2016, 17, 834–843. [Google Scholar] [CrossRef] [Green Version]
- Umrani, R.D.; Paknikar, K.M. Zinc oxide nanoparticles show antidiabetic activity in streptozotocin-induced type 1 and 2 diabetic rats. Nanomedicine 2014, 9, 89–104. [Google Scholar] [CrossRef]
- Alkaladi, A.; Abdelazim, A.M.; Afifi, M. Antidiabetic activity of zinc oxide and silver nanoparticles on streptozotocin-induced diabetic rats. Int. J. Mol. Sci. 2014, 15, 2015–2023. [Google Scholar] [CrossRef] [Green Version]
- Virgen-Ortiz, A.; Apolinar-Iribe, A.; Díaz-Reval, I.; Parra-Delgado, H.; Limón-Miranda, S.; Sánchez-Pastor, E.A.; Castro-Sánchez, L.; Castillo, S.J.; Dagnino-Acosta, A.; Bonales-Alatorre, E.; et al. Zinc Oxide Nanoparticles Induce an Adverse Effect on Blood Glucose Levels Depending on the Dose and Route of Administration in Healthy and Diabetic Rats. Nanomaterials 2020, 10, 2005. [Google Scholar] [CrossRef]
- Thornalley, P.J. Glycation in diabetic neuropathy: Characteristics, consequences, causes, and therapeutic options. Int. Rev. Neurobiol. 2002, 50, 37–57. [Google Scholar]
- Loeffler, D.A. Should development of Alzheimer’s disease-specific intravenous immunoglobulin be considered? J. Neuroinflamm. 2014, 11, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Reaven, G.M.; Thompson, L.W.; Nahum, D.; Haskins, E. Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care 1990, 13, 16–21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bottino, C.M.; Castro, C.C.; Gomes, R.L.; Buchpiguel, C.A.; Marchetti, R.L.; Neto, M.R. Volumetric MRI measurements can differentiate Alzheimer’s disease, mild cognitive impairment, and normal aging. Int. Psychogeriatr. 2002, 14, 59–72. [Google Scholar] [CrossRef]
- Padurariu, M.; Ciobica, A.; Hritcu, L.; Stoica, B.; Bild, W.; Stefanescu, C. Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci. Lett. 2010, 469, 6–10. [Google Scholar] [CrossRef] [PubMed]
- Yu, T.; Robotham, J.L.; Yoon, Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc. Natl. Acad. Sci. USA 2006, 103, 2653–2658. [Google Scholar] [CrossRef] [Green Version]
- Shen, C.; Chen, Y.; Liu, H.; Zhang, K.; Zhang, T.; Lin, A.; Jing, N. Hydrogen peroxide promotes Aβ production through JNK-dependent activation of γ-secretase. J. Biol. Chem. 2008, 283, 17721–17730. [Google Scholar] [CrossRef] [PubMed]
- Hodaei, H.; Adibian, M.; Nikpayam, O.; Hedayati, M.; Sohrab, G. The effect of curcumin supplementation on anthropometric indices, insulin resistance and oxidative stress in patients with type 2 diabetes: A randomized, double-blind clinical trial. Diabetol. Metab. Syndr. 2019, 11, 1–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ukperoro, J.U.; Offiah, N.; Idris, T.; Awogoke, D. Antioxidant effect of zinc, selenium and their combination on the liver and kidney of alloxan-induced diabetes in rats. Mediterr. J. Nutr. Metab. 2010, 3, 25–30. [Google Scholar] [CrossRef]
- El-Bahr, S.M.; Shousha, S.; Albokhadaim, I.; Shehab, A.; Khattab, W.; Ahmed-Farid, O.; El-Garhy, O.; Abdelgawad, A.; El-Naggar, M.; Moustafa, M.; et al. Impact of dietary zinc oxide nanoparticles on selected serum biomarkers, lipid peroxidation and tissue gene expression of antioxidant enzymes and cytokines in Japanese quail. BMC Vet. Res. 2020, 16, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Rahdar, A.; Hajinezhad, M.R.; Bilal, M.; Askari, F.; Kyzas, G.Z. Behavioral effects of zinc oxide nanoparticles on the brain of rats. Inorg. Chem. Commun. 2020, 119, 108131. [Google Scholar] [CrossRef]
- Dkhil, M.A.; Diab, M.S.; Aljawdah, H.M.; Murshed, M.; Hafiz, T.A.; Al-Quraishy, S.; Bauomy, A.A. Neuro-biochemical changes induced by zinc oxide nanoparticles. Saudi J. Biol. Sci. 2020, 27, 2863–2867. [Google Scholar] [CrossRef]
- Castranova, V. Signaling pathways controlling the production of inflammatory mediators in response to crystalline silica exposure: Role of reactive oxygen/nitrogen species. Free Radic. Biol. Med. 2004, 37, 916–925. [Google Scholar] [CrossRef]
- Boarescu, P.-M.; Boarescu, I.; Bocșan, I.C.; Gheban, D.; Bulboacă, A.E.; Nicula, C.; Pop, R.M.; Râjnoveanu, R.-M.; Bolboacă, S.D. Antioxidant and anti-inflammatory effects of Curcumin nanoparticles on drug-induced acute myocardial infarction in diabetic rats. Antioxidants 2019, 8, 504. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, Y.S.; Park, H.J.; Joo, S.Y.; Hong, M.H.; Kim, K.H.; Hong, Y.J.; Kim, J.H.; Park, H.W.; Jeong, M.H.; Cho, J.G.; et al. The protective effect of curcumin on myocardial ischemia-reperfusion injury. Korean Circ. J. 2008, 38, 353–359. [Google Scholar] [CrossRef]
- Gammoh, N.Z.; Rink, L. Zinc in infection and inflammation. Nutrients 2017, 9, 624. [Google Scholar] [CrossRef] [Green Version]
- Hassan, R.M.; Elsayed, M.; Kholief, T.E.; Hassanen, N.H.; Gafer, J.A.; Attia, Y.A. Mitigating effect of single or combined administration of nanoparticles of zinc oxide, chromium oxide, and selenium on genotoxicity and metabolic insult in fructose/streptozotocin diabetic rat model. ESPR 2021, 28, 1–18. [Google Scholar]
- Bettger, W.J.; O’Dell, B.L. A critical physiological role of zinc in the structure and function of biomembranes. Life Sci. 1981, 28, 1425–1438. [Google Scholar] [CrossRef]
- Attia, H.; Nounou, H.; Shalaby, M. Zinc oxide nanoparticles induced oxidative DNA damage, inflammation and apoptosis in rat’s brain after oral exposure. Toxics 2018, 6, 29. [Google Scholar] [CrossRef] [Green Version]
- Bai, Y.N.; Zheng, J.; Song Zf, D.Y.; Wen, Y. Effect of curcumin on expression of adiponectin in mice with insulin resistance. J. Shanghai Jiaotong Univ. Sci. 2013, 33, 136. [Google Scholar]
- Shao, W.; Yu, Z.; Chiang, Y.; Yang, Y.; Chai, T.; Foltz, W.; Lu, H.; Fantus, I.G.; Jin, T. Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS ONE 2012, 7, e28784. [Google Scholar] [CrossRef]
- Zhao, H.; Yenari, M.A.; Cheng, D.; Sapolsky, R.M.; Steinberg, G.K. Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity. J. Neurochem. 2008, 85, 1026–1036. [Google Scholar] [CrossRef]
- Zhao, Y.; Zhao, H.; Zhai, X.; Dai, J.; Jiang, X.; Wang, G.; Li, W.; Cai, L. Effects of Zn deficiency, antioxidants, and low-dose radiation on diabetic oxidative damage and cell death in the testis. Toxicol. Mech. Methods 2013, 23, 42–47. [Google Scholar] [CrossRef]
- Sharma, D.; Sethi, P.; Hussain, E.; Singh, R. Curcumin counteracts the aluminium-induced ageing-related alterations in oxidative stress, Na+, K+ ATPase and protein kinase C in adult and old rat brain regions. Biogerontology 2009, 10, 489–502. [Google Scholar] [CrossRef]
- Hamza, R.Z.; Al-Salmi, F.A.; El-Shenawy, N.S. Evaluation of the effects of the green nanoparticles zinc oxide on monosodium glutamate-induced toxicity in the brain of rats. PeerJ 2019, 7, e7460. [Google Scholar] [CrossRef] [Green Version]
- Saido, T.; Leissring, M.A. Proteolytic degradation of amyloid β-protein. Cold Spring Harb. Perspect. Med. 2012, 2, a006379. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Devi, L.; Ohno, M. PERK mediates eIF2α phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer’s disease. Neurobiol. Aging 2014, 35, 2272–2281. [Google Scholar] [CrossRef] [Green Version]
- Carrasquillo, M.M.; Belbin, O.; Zou, F.; Allen, M.; Ertekin-Taner, N.; Ansari, M.; Wilcox, S.L.; Kashino, M.R.; Ma, L.; Younkin, L.H.; et al. Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, Aß, and Alzheimer’s disease. PLoS ONE 2010, 5, e8764. [Google Scholar] [CrossRef]
- Hurley, L.L.; Akinfiresoye, L.; Nwulia, E.; Kamiya, A.; Kulkarni, A.A.; Tizabi, Y. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. Behav. Brain Res. 2013, 239, 27–30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, L.Y.; Tang, Z.J.; Han, Y.Z. Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane-induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK and PI3K/Akt signaling pathways. Mol. Med. Rep. 2016, 14, 3403–3412. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sweatt, J.D. The neuronal MAP kinase cascade: A biochemical signal integration system subserving synaptic plasticity and memory. J. Neurochem. 2001, 76, 1–10. [Google Scholar] [CrossRef]
- Avila, J. Tau kinases and phosphatases. J. Cell Mol. Med. 2008, 12, 258–259. [Google Scholar] [CrossRef] [Green Version]
- Lee, K.M.; Bang, J.; Kim, B.Y.; Lee, I.S.; Han, J.S.; Hwang, B.Y.; Jeon, W.K. Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling. BMC Complement. Altern. Med. 2015, 15, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Wang, B.; Li, W.; Jin, H.; Nie, X.; Shen, H.; Li, E.; Wang, W. Curcumin attenuates chronic intermittent hypoxia-induced brain injuries by inhibiting AQP4 and p38 MAPK pathway. Respir. Physiol. Neurobiol. 2018, 255, 50–57. [Google Scholar] [CrossRef] [PubMed]
- Jung, K.K.; Lee, H.S.; Cho, J.Y.; Shin, W.C.; Rhee, M.H.; Kim, T.G.; Kang, J.H.; Kim, S.H.; Hong, S.; Kang, S.Y. Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia. Life Sci. 2006, 79, 2022–2031. [Google Scholar] [CrossRef]
- Amin, S.N.; Younan, S.M.; Youssef, M.F.; Rashed, L.A.; Mohamady, I. A histological and functional study on hippocampal formation of normal and diabetic rats. F1000Research 2013, 2, 151. [Google Scholar] [CrossRef] [Green Version]
Groups | Fasting Blood Glucose (mg/dL) | Insulin (µU/mL) | HOMA-IR | Serum AGEs (ng/mg Protein) |
---|---|---|---|---|
Control | 106.80 ± 0.66 c | 14.72 ± 0.22 d | 3.88 ± 0.06 e | 12.34 ± 0.03 d |
HFD/STZ | 489.20 ± 1.80 a | 169.60 ± 1.40 a | 204.85 ± 1.70 a | 33.21 ± 0.01 a |
HFD/STZ-Cur | 88.80 ± 0.58 d | 57.24 ± 0.30 c | 12.55 ± 0.12 c,d | 22.41 ± 0.01 b |
HFD/STZ-CurNP-10 | 89.20 ± 0.37 d | 71.24 ± 0.56 b | 15.68 ± 0.12 c | 14.31 ± 0.06 c,d |
HFD/STZ-CurNP-50 | 92.20 ± 0.86 d | 68.76 ± 0.40 b | 15.65 ± 0.13 c | 17.99 ± 0.02 c |
HFD/STZ-Zinc sulfate | 119.00 ± 1.20 b | 70.58 ± 0.50 b | 20.74 ± 0.33 b | 25.41 ± 0.02 b |
HFD/STZ-ZnONP-10 | 75.60 ± 0.50 e | 60.58 ± 0.45 c | 11.30 ± 0.12 d | 20.32 ± 0.04 b |
HFD/STZ-ZnONP-50 | 89.80 ± 0.37 d | 69.34 ± 0.60 b | 15.37 ± 0.14 c | 15.67 ± 0.03 c |
HFD/STZ-Metformin | 70.60 ± 0.93 e | 61.22 ± 0.26 c | 10.67 ± 0.12 d | 21.34 ± 0.05 b |
Groups | TBARS (µmoL/mg Protein) | NO (µmoL/mg Protein) | CAT (U/mg Protein) | SOD | GPx | GST | GSH (µmoL/mg Protein) |
---|---|---|---|---|---|---|---|
(µmoL/min/mg Protien) | |||||||
Control | 174.29 ± 5.11 d | 0.80 ± 0.04 c | 0.04 ± 0.00 d | 105.63 ± 5.40 g | 44.28 ± 0.08 a | 40.10 ± 0.10 c | 24.31 ± 1.32 e |
HFD/STZ | 381.07 ± 24.50 a | 5.41 ± 0.01 a | 0.01 ± 0.00 f | 18.89 ± 2.00 i | 19.42 ± 0.14 c | 10.44 ± 0.30 f | 8.06 ± 0.90 f |
HFD/STZ-Cur | 188.95 ± 5.56 d | 0.64 ± 0.02 c | 0.04 ± 0.00 d | 121.30 ± 11.70 f | 38.3 ± 0.09 b | 36.22 ± 0.50 d | 33.23 ± 0.90 d |
HFD/STZ-CurNP-10 | 148.19 ± 5.94 f | 0.52 ± 0.01 d | 0.10 ± 0.00 a | 733.31 ± 10.15 a | 47.58 ± 0.12 a | 77.30 ± 0.40 a | 71.78 ± 2.35 a |
HFD/STZ-CurNP-50 | 165.54 ± 15.41 e | 0.71 ± 0.03 c | 0.06 ± 0.00 c | 380.48 ± 7.50 c | 44.14 ± 0.07 a | 65.33 ± 0.30 b | 60.18 ± 2.36 b |
HFD/STZ-Zinc sulfate | 226.20 ± 7.76 c | 0.61 ± 0.02 c,d | 0.04 ± 0.00 d | 84.82 ± 7.88 h | 33.26 ± 0.10 b | 25.43 ± 0.20 e | 36.45 ± 1.70 d |
HFD/STZ-ZnONP-10 | 177.88 ± 5.35 d | 0.77 ± 0.04 c | 0.06 ± 0.00 c | 227.82 ± 7.50 d | 40.12 ± 0.05 a | 50.43 ± 0.10 c | 55.97 ± 1.80 b |
HFD/STZ-ZnONP-50 | 158.05 ± 6.90 e | 0.66 ± 0.03 c | 0.08 ± 0.00 b | 529.68 ± 24.40 b | 44.78 ± 0.65 a | 60.33 ± 0.50 b | 65.00 ± 2.90 a |
HFD/STZ-Metformin | 250.51 ± 4.00 b | 1.27 ± 0.02 b | 0.02 ± 0.00 e | 160.35 ± 16.32 e | 35.68 ± 0.15 b | 34.55 ± 0.50 d | 47.86 ± 0.90 c |
Groups | Adiponectin (ng/mL) | Leptin (ng/mL) | IL-6 (ng/mg Protein) | TNF-α (ng/mg Protein) |
---|---|---|---|---|
Control | 7.46 ± 0.17 b | 15.56 ± 0.08 c | 17.45 ± 0.023 e | 4.63 ± 0.02 e |
HFD/STZ | 3.40 ± 0.23 d | 29.70 ± 0.15 a | 68.45 ± 0.03 a | 47.36 ± 0.04 a |
HFD/STZ-Cur | 5.63 ± 0.22 c | 23.56 ± 0.12 b | 26.41 ± 0.02 d | 15.34 ± 0.02 c |
HFD/STZ-CurNP-10 | 6.63 ± 0.15 b | 21.23 ± 0.16 b | 22.60 ± 0.02 e | 9.43 ± 0.01 d |
HFD/STZ-CurNP-50 | 7.93 ± 0.26 b | 16.63 ± 0.25 c | 25.71 ± 0.02 d | 14.03 ± 0.01 c |
HFD/STZ-Zinc sulfate | 5.46 ± 0.06 c | 25.63 ± 0.17 b | 55.34 ± 0.02 b | 22.85 ± 0.04 b |
HFD/STZ-ZnONP-10 | 7.10 ± 0.11 b | 17.63 ± 0.18 c | 31.24 ± 0.03 d | 17.53 ± 0.01 b |
HFD/STZ-ZnONP-50 | 9.03 ± 0.19 a | 19.00 ± 0.12 c | 24.30 ± 0.01 d | 10.95 ± 0.04 d |
HFD/STZ-Metformin | 6.27 ± 0.03 b | 22.30 ± 0.17 b | 43.11 ± 0.01 c | 19.83 ± 0.02 b |
Groups | AChE (mmoL/min/mg Protein) | IDE (ng/mg Protein) | Hippocampal Aβ-42 (ng/mg Protein) |
---|---|---|---|
Control | 15.58 ± 0.30 b | 30.10 ± 0.05 a | 23.43 ± 0.01 f |
HFD/STZ | 84.01 ± 4.10 a | 7.12 ± 0.01 c | 140.87 ± 0.34 a |
HFD/STZ-Cur | 17.37 ± 0.57 b | 23.00 ± 0.01 b | 52.00 ± 0.00 d |
HFD/STZ-CurNP-10 | 12.16 ± 0.14 c | 24.24 ± 0.12 a,b | 31.53 ± 0.02 e |
HFD/STZ-CurNP-50 | 14.60 ± 0.47 b | 29.16 ± 0.08 a | 37.42 ± 0.01 e |
HFD/STZ-Zinc sulfate | 16.63 ± 0.46 b | 17.09 ± 0.00 b | 101.33 ± 0.02 b |
HFD/STZ-ZnONP-10 | 17.02 ± 0.49 b | 27.17 ± 0.09 a | 72.55 ± 0.01 c |
HFD/STZ-ZnONP-50 | 11.30 ± 0.80 c | 25.08 ± 0.04 a | 33.06 ± 0.03 e |
HFD/STZ-Metformin | 11.12 ± 0.54 c | 22.04 ± 0.02 b | 60.03 ± 0.02 c |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Abdulmalek, S.; Nasef, M.; Awad, D.; Balbaa, M. Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats. Pharmaceutics 2021, 13, 1937. https://doi.org/10.3390/pharmaceutics13111937
Abdulmalek S, Nasef M, Awad D, Balbaa M. Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats. Pharmaceutics. 2021; 13(11):1937. https://doi.org/10.3390/pharmaceutics13111937
Chicago/Turabian StyleAbdulmalek, Shaymaa, Mayada Nasef, Doaa Awad, and Mahmoud Balbaa. 2021. "Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats" Pharmaceutics 13, no. 11: 1937. https://doi.org/10.3390/pharmaceutics13111937
APA StyleAbdulmalek, S., Nasef, M., Awad, D., & Balbaa, M. (2021). Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats. Pharmaceutics, 13(11), 1937. https://doi.org/10.3390/pharmaceutics13111937