Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 12, December, p. 1609–1614

doi: 10.17219/acem/110328

Publication type: original article

Language: English

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Aged garlic extract and S-allylcysteine increase the GLUT3 and GCLC expression levels in cerebral ischemia

Carlos Daniel Gomez1,B,C,F, Penélope Aguilera2,B,C,F, Alma Ortiz-Plata3,B,F, Felipe Nares López2,C,D,F, María Elena Chánez-Cárdenas2,D,E,F, Eugenia Flores-Alfaro4,C,F, Martha Eugenia Ruiz-Tachiquín5,C,F, Monica Espinoza-Rojo6,A,B,D,F

1 Department of Physiology and Pharmacology, University of Calgary, Canada

2 Laboratory of Cerebral Vascular Pathology, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Mexico City, Mexico

3 Laboratory of Experimental Neuropathology, National Institute of Neurology and Neurosurgery, Mexico City, Mexico

4 Laboratory of Clinical and Molecular Epidemiology, Faculty of Biological and Chemical Sciences, Universidad Autónoma de Guerrero, Chilpancingo, Mexico

5 Medical Research Unit on Human Genetics, Pediatrics Hospital, Mexican Institute of Social Security (IMSS), Mexico City, Mexico

6 Laboratory of Molecular and Genomic Biology, Faculty of Biological Chemical Sciences, Universidad Autónoma de Guerrero, Chilpancingo, Mexico

Abstract

Background. During cerebral ischemia, energy restoration through the regulation of glucose transporters and antioxidant defense mechanisms is essential to maintain cell viability. Antioxidant therapy has been considered effective to attenuate brain damage; moreover, the regulation of transcription factors that positively regulate the expression of glucose transporters is associated with this therapy. Recently, it has been reported that the use of antioxidants such as S-allylcysteine (SAC), a component of aged garlic extract (AGE), improves survival in experimental models of cerebral ischemia.
Objectives. The aim of this study was to determine the effect of AGE and SAC on the level of mRNA expression of the main neuronal glucose transporter (GLUT3) and the glutamate cysteine ligase catalytic subunit (GCLC) in rats with transient focal cerebral ischemia.
Material and Methods. Cerebral ischemia was induced in male Wistar rats by middle cerebral artery occlusion (MCAO) for 2 h. The animals were sacrificed after different reperfusion times (0–48 h). Animals injected with AGE (360 mg/kg, intraperitoneally (i.p.)) and SAC (300 mg/kg, i.p.) at the beginning of reperfusion were sacrificed after 2 h. The mRNA expression level was analyzed in the fronto-parietal cortex using quantitative polymerase chain reaction (qPCR).
Results. Two major increases in GLUT3 expression at 1 h and 24 h of reperfusion were found. Both treatments increased GLUT3 and GCLC mRNA levels in control and under ischemic/reperfusion injury animals.
Conclusion. This data suggests that SAC and AGE might induce neuroprotection, while controlling reactive oxygen species (ROS) levels, as indicated by the increase in GCLC expression, and regulating the energy content of the cell by increasing glucose transport mediated by GLUT3.

Key words

antioxidants, cerebral ischemia, glucose transporters

References (38)

  1. Starkov A, Chinopoulos C, Fiskum G. Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury. Cell Calcium. 2004;36(3–4):257–264.
  2. Zhang R, Xu M, Wang Y, Xie F, Zhang G, Qin X. Nrf2: A promising therapeutic target for defensing against oxidative stress in stroke. Mol Neurobiol. 2017;54(8):6006–6017.
  3. Fraser PA. The role of free radical generation in increasing cerebrovascular permeability. Free Radic Biol Med. 2011;51(5):967–977.
  4. Numagami Y, Sato S, Ohnishi ST. Attenuation of rat ischemic brain damage by aged garlic extracts: A possible protecting mechanism as antioxidants. Neurochem Int. 1996;29(2):135–143.
  5. Aguilera P, Chánez-Cardenas ME, Ortiz-Plata A, et al. Aged garlic extract delays the appearance of infarct area in a cerebral ischemia model, an effect likely conditioned by the cellular antioxidant systems. Phytomedicine. 2010;17(3–4):241–247.
  6. Ashafaq M, Khan MM, Raza SS, et al. S-allyl cysteine mitigates oxidative damage and improves neurologic deficit in a rat model of focal cerebral ischemia. Nutr Res. 2012;32(2):133–143.
  7. Wilson WJ, Poellinger L. The dietary flavonoid quercetin modulates HIF-1α activity in endothelial cells. Biochem Biophys Res Commun. 2002;293(1):446–450.
  8. Zhang B, Tanaka J, Yang L, et al. Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1. Neuroscience. 2004;126(2):433–440.
  9. Doung TT, Chami B, McMahon AC, et al. Pre-treatment with the synthetic antioxidant T-butyl bisphenol protects cerebral tissues from experimental ischemia reperfusion injury. J Neurochem. 2014;130(6):733–747.
  10. Simpson IA, Dwyer D, Malide D, Moley KH, Travis A, Vannucci SJ. The facilitative glucose transporter GLUT3: 20 years of distinction. Am J Physiol Endocrinol Metab. 2008;295(2):E242–E253.
  11. Barron CC, Bilan PJ, Tsakiridis T, Tsiani E. Facilitative glucose transporters: Implications for cancer detection, prognosis and treatment. Metabolism. 2016;65(2):124–139.
  12. Wu F, Wu J, Nicholson AD, Echeverry R, et al. Tissue-type plasminogen activator regulates the neuronal uptake of glucose in the ischemic brain. J Neurosci. 2012;32(29):9848–9858.
  13. Park SM, Lee JC, Chen BH, et al. Difference in transient ischemia induced neuronal damage and glucose transporter-1 immunoreactivity in the hippocampus between adult and young gerbils. Iran J Basic Med Sci. 2016;19(5):521–528.
  14. Vannucci SJ, Seaman LB, Vannucci RC. Effects of hypoxia-ischemia on GLUTI and GLUT3 glucose transporters in immature rat brain. J Cereb Blood Flow Metab. 1996;16(1):77–81.
  15. Ide N, Lau BH. Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation. J Nutr. 2001;131(3s):1020S–1026S.
  16. Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. Glutathione defense mechanism in liver injury: Insights from animal models. Food Chem Toxicol. 2013;60:38–44.
  17. Rawal AK, Muddeshwar MG, Biswas SK. Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation. BMC Complement Altern Med. 2004;4:11.
  18. Guan D, Su Y, Li Y, et al. Tetramethylpyrazine inhibits CoCl2-induced neurotoxicity through enhancement of Nrf2/GCLc/GSH and suppression of HIF1α/NOX2/ROS pathways. J Neurochem. 2015;134(3):551–565.
  19. Numagami Y, Ohnishi ST. S-allylcysteine inhibits free radical production, lipid peroxidation and neuronal damage in rat brain ischemia. J Nutr. 2001;131(3s):1100S–1105S.
  20. Qu Z, Mossine VV, Cui J, Sun GY, Gu Z. Protective effects of AGE and its components on neuroinflammation and neurodegeneration. Neuro­mol Med. 2016;18(3):474–482.
  21. Maldonado PD, Alvarez-Idaboy JR, Aguilar-Gonzalez A, et al. Role of allyl group in the hydroxyl and peroxyl radical scavenging activity of S-allylcysteine. J Phys Chem B. 2011;115(45):13408–13417.
  22. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20(1):84–91
  23. Yager JY, Brucklacher RM, Vannucci RC. Cerebral energy metabolism during hypoxia-ischemia and early recovery in immature rats. Am J Physiol. 1992;262(3 Pt 2):H672–H677.
  24. Thoren AE, Helps SC, Nilsson M, Sims NR. The metabolism of 14C-glucose by neurons and astrocytes in brain subregions following focal cerebral ischemia in rats. J Neurochem. 2006;97(4):968–978.
  25. Vannucci RC, Yager JY, Vannucci SJ. Cerebral glucose and energy utilization during the evolution of hypoxic-ischemic brain damage in the immature rat. J Cereb Blood Flow Metab. 1994;14(2):279–288.
  26. Espinoza-Rojo M, Iturralde-Rodriguez KI, Chanez-Cardenas ME, Ruiz Tachiquin ME, Aguilera P. Glucose transporters regulation on ischemic brain: Possible role as therapeutic target. Cent Nerv Syst Agents Med Chem. 2010;10(4):317–325.
  27. Patching SG. Glucose transporters at the blood-brain barrier: Function, regulation and gateways for drug delivery. Mol Neurobiol. 2017;54(2):1046–1077.
  28. Rajakumar A, Thamotharan S, Raychaudhuri N, Menon RK, Devaskar SU. Trans-activators regulating neuronal glucose transporter isoform-3 gene expression in mammalian neurons. J Biol Chem. 2004;279(25):26768–26779.
  29. Pugazhenthi S, Nesterova A, Sable C, et al. Akt/Protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem. 2000;275(15):10761–10766.
  30. Ma Y, Lu C, Li C, et al. Overexpression of HSPA12B protects against cerebral ischemia/reperfusion injury via a PI3K/Akt-dependent mechanism. Biochim Biophys Acta. 2013;1832(1):57–66.
  31. Iwabuchi S, Kawahara K. Inducible astrocytic glucose transporter-3 contributes to the enhanced storage of intracellular glycogen during reperfusion after ischemia. Neurochem Int. 2011;59(2):319–325.
  32. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxy­lases that modify HIF. Science. 2001;294(5545):1337–1340.
  33. Shin JA, Lee KE, Kim HS, Park EM. Acute resveratrol treatment modulates multiple signaling pathways in the ischemic brain. Neurochem Res. 2012;37(12):2686–2696.
  34. Cervantes MI, de Oca Balderas PM, Gutierrez-Baños J, et al. Comparison of antioxidant activity of hydroethanolic fresh and aged garlic extracts and their effects on cerebral ischemia. Food Chem. 2013;140(1–2):343–352.
  35. Colin-Gonzalez AL, Santana RA, Silva-Islas CA, Chanez-Cardenas ME, Santamaria A, Maldonado PD. The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine-induced protection. Oxid Med Cell Longev. 2012;2012:907162.
  36. Bayan L, Koulivand PH, Gorji A. Garlic: A review of potential therapeutic effects. Avicenna J Phytomed. 2014;4(1):1–14
  37. Zimmermann C, Winnefeld K, Streck S, Roskos M, Haberl RL. Antioxidant status in acute stroke patients and patients at stroke risk. Eur Neurol. 2004;51(3):157–161.
  38. Sethy NK, Singh M, Kumar R, Ilavazhagan G, Bhargava K. Upregulation of transcription factor NRF2-mediated oxidative stress response pathway in rat brain under short-term chronic hypobaric hypoxia. Funct Integr Genomics. 2011;11(1):119–137.
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