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Gamma Amino Butyric Acid Attenuates Brain Oxidative Damage Associated with Insulin Alteration in Streptozotocin-Treated Rats

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Abstract

The aim of the current study was to evaluate the role of γ-amino butyric acid (GABA) in insulin disturbance and hyperglycemia associated with brain oxidative damage in streptozotocin-treated rats. Streptozotocin (STZ) was administered to male albino rats as a single intraperitoneal dose (60 mg/kg body weight). GABA (200 mg/Kg body weight/day) was administered daily via gavages during 3 weeks to STZ-treated-rats. Male albino rats Sprague–Dawley (10 ± 2 weeks old; 120 ± 10 g body weight) were divided into 4 groups of 6 rats and treated in parallel. (1) Control group: received distilled water, (2) GABA group: received GABA, (3) STZ group: STZ-treated rats received distilled water, (4) STZ + GABA group: STZ-treated rats received GABA. Rats were sacrificed after a fasting period of 12 h next last dose of GABA. The results obtained showed that STZ-treatment produced hyperglycemia and insulin deficiency (similar to type1 Diabetes). These changes were associated with oxidative damage in brain tissue and notified by significant decreases of superoxide dismutase and catalase activities in parallel to significant increases of malondialdehyde and advanced oxidation protein products levels. The histopathology reports also revealed that STZ-treatment produced degeneration of pancreatic cells. The administration of GABA to STZ-treated rats preserved pancreatic tissue with improved insulin secretion, improved glucose level and minimized oxidative stress in brain tissues. It could be concluded that GABA might protect the brain from oxidative stress and preserve pancreas tissues with adjusting glucose and insulin levels in Diabetic rats and might decrease the risk of neurodegenerative disease in diabetes.

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References

  1. Chintan AP, Nimish LP, Nayana B, Bhavna M, Mahendra G, Hardik T. Cardiovascular complication of diabetes mellitus. J Appl Pharm Sci. 2011;4:1–6.

    Google Scholar 

  2. Haskins K, Bradley B, Powers K. Oxidative stress in type 1 diabetes. Ann N Y Acad Sci. 2003;1005:43–54.

    Article  CAS  PubMed  Google Scholar 

  3. Piconi L, Quagliaro L, Ceriello A. Oxidative stress in diabetes. Clin Chem Lab Med. 2003;41:1144–9.

    Article  CAS  PubMed  Google Scholar 

  4. Wang JY, Zhu C, Qian TW, Guo H, Wang DD, Zhang F, et al. Extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in mice. Exp Ther Med. 2015;9(1):43–8.

    PubMed  Google Scholar 

  5. Francis GJ, Martinez JA, Liu WQ, Xu K, Ayer A, Fine J, et al. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabeticencephalopathy. Brain. 2008;131(12):3311–34.

    Article  PubMed  Google Scholar 

  6. Zhou Y, Luo Y, Dai J. Axonal and dendritic changes are associated with diabetic encephalopathy in rats: an important risk factor for Alzheimer’s disease. J Alzheimers Dis. 2013;34:937–47.

    CAS  PubMed  Google Scholar 

  7. Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH. Ageing and diabetes: implications for brain function. Eur. J Pharmacol. 2002;441:1–14.

    CAS  PubMed  Google Scholar 

  8. Baquer NZ, Taha A, Kumar P, McLean P, Cowsik SM, Kale RK, et al. A metabolic and functional overview of brain aging linked to neurological disorders. Biogerontology. 2009;10(4):377–413.

    Article  CAS  PubMed  Google Scholar 

  9. Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X, et al. The effects of physical activity, education, and body mass index on the aging brain. Hum Brain Mapp. 2011;32(9):1371–82.

    Article  PubMed  Google Scholar 

  10. Sun J, Chen Y, Li M, Ge Z. Role of antioxidant enzymes on ionizing radiation resistance. Free Radic Biol Med. 1998;24:586–93.

    Article  CAS  PubMed  Google Scholar 

  11. Starkov AA, Chinopoulos C, Fiskum G. Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury. Cell Calcium. 2004;36:257–64.

    Article  CAS  PubMed  Google Scholar 

  12. Migliore L, Coppede F. Environmental-induced oxidative stress in neurodegenerative disorders and aging. Mutat Res. 2009;674:73–84.

    Article  CAS  PubMed  Google Scholar 

  13. Mohamadin AM, Sheikh B. Abd El-Aal AA, Elberry AA, Al-Abbasi FA. Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions. Pest Biochem Physiol. 2010;98:128–34.

    Article  CAS  Google Scholar 

  14. Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress and antioxidants: a review. J Biochem Mol Toxic. 2003;17:24–38.

    Article  CAS  Google Scholar 

  15. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol. 2002;213:1–47.

    Article  CAS  PubMed  Google Scholar 

  16. Luscher B, Keller CA. Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses. Pharmacol Ther. 2004;102:195–221.

    Article  CAS  PubMed  Google Scholar 

  17. Billinton A, Ige AO, Bolam JP, White JH, Marshall FH, Emson PC. Advances in the molecular understanding of GABAB receptors. Trends Neurosci. 2001;24:277–82.

    Article  CAS  PubMed  Google Scholar 

  18. Chebib M, Johnston GA. The ‘ABC’ of GABA receptors: a brief review. Clin Exp Pharmacol Physiol. 1999;26:937–40.

    Article  CAS  PubMed  Google Scholar 

  19. Krnjevic K. How does a little acronym become a big transmitter? Biochem Pharmacol. 2004;68:1549–55.

    Article  CAS  PubMed  Google Scholar 

  20. Bowery NG. GABAB receptor: a site of therapeutic benefit. Curr Opin Pharmacol. 2006;6:37–43.

    Article  CAS  PubMed  Google Scholar 

  21. Soi-ampornkul R, Junnu S, Kanyok S, Liammongkolkul S, Katanyoo W, Umpornsirirat S. Antioxidative and neuroprotective activities of the pre-germinated brown rice extract. Food Nutr Sci. 2012;3(1):135–40. doi:10.4236/fns.2012.31020.

    Article  CAS  Google Scholar 

  22. Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nat Rev Neurosci. 2002;3(9):715–27.

    Article  CAS  PubMed  Google Scholar 

  23. Minuk GY. Gamma-aminobutyric acid and the liver. Dig Dis. 1993;11(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  24. Erdo SL, Wolf JR. γ-Aminobutyric acid outside the mammalian brain. J Neurochem. 1990;54:363–72.

    Article  CAS  PubMed  Google Scholar 

  25. Braun M, Ramracheya R, Bengtsson M, Clark A, Walker JN, Johnson PR, et al. Gamma-aminobutyric acid (GABA) is an autocrine excitatory transmitter in human pancreatic beta-cells. Diabetes. 2010;59:1694–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bergersen LH, Storm-Mathisen J, Gundersen V. Immunogold quantification of amino acids and proteins in complex subcellular compartments. Nat Protoc. 2008;3:144–52.

    Article  CAS  PubMed  Google Scholar 

  27. Erejuwa OO, Sulaiman SA, Wahab MSA, Sirajudeen KNS, Salleh MSM, Gurtu S. Glibenclamide or metformin combined with honey improves glycemic control in streptozotocin-induced diabetic rats. Int J Biol Sci. 2011;72:244–52.

    Article  Google Scholar 

  28. Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi S, Farhangi A, Allah A, et al. Induction of diabetes by streptozotocin in rats. Indian J Clin Biochem. 2007;22(2):60–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nakagawa T, Yokozawa T, Kim HJ, Shibahara N. Protective effect of gamma aminobutyric acid in rats with streptozotocin-induced diabetes. J Nutr Sci Vitaminol. 2005;51:278–82.

    Article  CAS  PubMed  Google Scholar 

  30. Mikesh LM, Bruns DE. Stabilization of glucose in blood specimens: mechanism of delay in fluoride inhibition of glycolysis. Clin Chem. 2008;54(5):930–2.

    Article  CAS  PubMed  Google Scholar 

  31. Trinder P. Enzymatic colorimetric determination of glucose. Ann Clin Biochem. 1969;6(2):24–7.

    Article  CAS  Google Scholar 

  32. Clark PMS, Hales CN. How to measure plasma insulin. Diabetes Metab Rev. 1994;10:79–90.

    Article  CAS  PubMed  Google Scholar 

  33. Yoshioka T, Kawada K, Shimada T, Mori M. Lipid peroxidation in maternal and cord blood and protective mechanism against activated oxygen toxicity in the blood. Am J Obstet Gynecol. 1979;135:372–6.

    Article  CAS  PubMed  Google Scholar 

  34. Witko-Sarsat V, Friendlander M, Capelliere-Blandin C, Nguyen-KhoaT Zing J, Jungers P, et al. Advanced oxidation protein products as a noval marker of oxidative stress in uremia. Kidney Int. 1996;49:1304–13.

    Article  CAS  PubMed  Google Scholar 

  35. Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun. 1972;46:849–54.

    Article  CAS  PubMed  Google Scholar 

  36. Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389–94.

    Article  CAS  PubMed  Google Scholar 

  37. Bancroft JD, Gamble M. Theory and practice of histological techniques. In: 5th ed. Edinburgh. New York, London, Philadelphia, Churchill Livingstone Pub; 2002. pp. 172–175 and 593–620.

  38. Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med. 2012;237:481–90.

    Article  CAS  Google Scholar 

  39. Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, et al. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes. 1999;48(4):927–32.

    Article  CAS  PubMed  Google Scholar 

  40. Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress and antioxidants: a review. J Biochem Mol Toxicol. 2003;17:24–38.

    Article  CAS  PubMed  Google Scholar 

  41. Young TA, Cunningham CC, Bailey SM. Reactive oxygen species production by the mitochondrial respiratory chain in isolated rat hepatocytes and liver mitochondria: studies using myxothiazol. Arch Biochem Biophys. 2002;405(1):65–72.

    Article  CAS  PubMed  Google Scholar 

  42. Bergamini CM, Gambetti S, Dondi A, Cervellati C. Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des. 2004;10(14):1611–26.

    Article  CAS  PubMed  Google Scholar 

  43. Davi G, Falco A, Patrono C. Lipid peroxidation in diabetes mellitus. Antioxid Redox Signal. 2005;7:256–68.

    Article  CAS  PubMed  Google Scholar 

  44. Yoshida S, Hashimoto T, Kihara M, Imai N, Yasuzaki H, Nomura K, et al. Urinary oxidative stress markers closely reflect the efficacy of Candesartan treatment for diabetic nephropathy. Nephron Exp Nephrol. 2008;111:20–30.

    Article  Google Scholar 

  45. Sadi G, Yilmaz O, Güray T. Effect of vitamin C and lipoic acid on streptozotocin-induced diabetes gene expression: mRNA and protein expressions of Cu–Zn SOD and catalase. Mol Cell Biochem. 2008;309:109–16.

    Article  CAS  PubMed  Google Scholar 

  46. Sadi G, Guray T. Gene expressions of Mn-SOD and GPx-1 in streptozotocin-induced diabetes: effect of antioxidants. Mol Cell Biochem. 2009;327:127–34.

    Article  CAS  PubMed  Google Scholar 

  47. Matsunami T, Sato Y, Sato T, Ariga S, Shimomura T, Yukawa M. Oxidative stress and gene expression of antioxidant enzymes in the streptozotocin-induced diabetic rats under hyperbaric oxygen exposure. Int J Clin Exp Pathol. 2010;3(2):177–88.

    CAS  Google Scholar 

  48. Yoshikuni Y. FDA GRAS Notice for gamma-amino butyric acid (GABA). Kyoto: Pharma Foods International Co. Ltd; 2008.

    Google Scholar 

  49. Palak P, Dipa I. GABA as potential target in the treatment of Type-1 diabetes mellitus. IAJPR. 2013; 3(3):2636–2642. www.scopemed.org/?mno=155108. Accessed 11 July 2016.

  50. Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, et al. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proc Natl Acad Sci. 2011;108(28):11692–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Purwana I, Zheng J, Li X, Deurloo M, Son DO, Zhang Z, et al. GABA promotes human β-cell proliferation and modulates glucose homeostasis. Diabetes. 2014;63(12):4197–205. doi:10.2337/db14-0153 Epub 2014 Jul 9.

    Article  CAS  PubMed  Google Scholar 

  52. Bansal P, Wang S, Liu S, Xiang YY, Lu WY, Wang Q. GABA coordinates with insulin in regulating secretory function in pancreatic INS-1 β-cells. PLoS One. 2011;6(10):26225.

    Article  Google Scholar 

  53. Xu E, Kumar M, Zhang Y, Ju W, Obata T, Zhang N, et al. Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system. Cell Metab. 2006;3:47–58.

    Article  CAS  PubMed  Google Scholar 

  54. Hou CW. Pu-Erh tea and GABA attenuates oxidative stress in kainic acid-induced status epilepticus. J Biomed Sci. 2011;18:75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Deng Y, Wang W, Yu P, Xi Z, Xu L, Li X, et al. Comparison of taurine, GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo. Nanoscale Res Lett. 2013;8:190.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Sasaki S, Yokozawa T, Cho EJ, Oowada S, Kim M. Protective role of gamma-aminobutyric acid against chronic renal failure in rats. J Pharm Pharmacol. 2006;11:1515–25.

    Article  Google Scholar 

  57. Liu B, Barbosa-Sampaio H, Jones PM, Persaud SJ, Muller DS. The CaMK4/CREB/IRS-2 cascade stimulates proliferation and inhibits apoptosis of β-cells. PLoS One. 2012;7(9):e45711. doi:10.1371/journal.pone.0045711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Prud’homme GJ, Glinka Y, Udovyk O, Hasilo C, Paraskevas S, Wang Q. GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity. Biochem Biophys Res Commun. 2014;452(3):649–54.

    Article  PubMed  Google Scholar 

  59. Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, et al. oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PLoS One. 2011;6(9):25338.

    Article  Google Scholar 

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  1. Radiation Biology Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt

    N. A. Eltahawy, H. N. Saada & A. S. Hammad

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  1. N. A. Eltahawy
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Eltahawy, N.A., Saada, H.N. & Hammad, A.S. Gamma Amino Butyric Acid Attenuates Brain Oxidative Damage Associated with Insulin Alteration in Streptozotocin-Treated Rats. Ind J Clin Biochem 32, 207–213 (2017). https://doi.org/10.1007/s12291-016-0597-2

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