Abstract
Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abd El-Twab SM, Mohamed HM, Mahmoud AM (2016) Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis. Can J Physiol Pharmacol 94:651–661. doi:10.1139/cjpp-2015-0503
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Agca CA, Tuzcu M, Hayirli A, Sahin K (2014) Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats. Food Chem Toxicol 71:116–121. doi:10.1016/j.fct.2014.05.023
Alvarez-Nölting R, Arnal E, Barcia JM et al (2012) Protection by DHA of early hippocampal changes in diabetes: possible role of CREB and NF-κB. Neurochem Res 37:105–115. doi:10.1007/s11064-011-0588-x
Anderson RJ, Freedland KE, Clouse RE, Lustman PJ (2001) The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24:1069–1078. doi:10.2337/diacare.24.6.1069
Biswas SK (2016) Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev 2016:1–9. doi:10.1155/2016/5698931
Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289–298
Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820. doi:10.1038/414813a
Burlinson B, Tice RR, Speit G et al (2007) Fourth International Workgroup on Genotoxicity testing: results of the in vivo Comet assay workgroup. Mutat Res 627:31–35. doi:10.1016/j.mrgentox.2006.08.011
Cade WT (2008) Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 88:1322–1335. doi:10.2522/ptj.20080008
Caletti G, Olguins DB, Pedrollo EF et al (2012) Antidepressant effect of taurine in diabetic rats. Amino Acids 43:1525–1533. doi:10.1007/s00726-012-1226-x
Caletti G, Almeida FB, Agnes G et al (2015) Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats. Behav Brain Res 283:11–15. doi:10.1016/j.bbr.2015.01.018
Chen W, Guo J, Zhang Y, Zhang J (2016) The beneficial effects of taurine in preventing metabolic syndrome. Food Funct 7:1849–1863. doi:10.1039/C5FO01295C
Datusalia AK, Sharma SS (2014) Amelioration of diabetes-induced cognitive deficits by GSK-3β inhibition is attributed to modulation of neurotransmitters and neuroinflammation. Mol Neurobiol 50:390–405. doi:10.1007/s12035-014-8632-x
De Luca G, Calpona PR, Caponetti A et al (2001) Taurine and osmoregulation: platelet taurine content, uptake, and release in type 2 diabetic patients. Metabolism 50:60–64. doi:10.1053/meta.2001.19432
De Winter F-L, Emsell L, Bouckaert F et al (2017) No association of lower hippocampal volume with alzheimer’s disease pathology in late-life depression. Am J Psychiatry 174:237–245. doi:10.1176/appi.ajp.2016.16030319
Devaraj S, Glaser N, Griffen S et al (2006) Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 55:774–779
Devasagayam TPA, Tilak JC, Boloor KK et al (2004) Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India 52:794–804
Duarte JMN, Carvalho RA, Cunha RA, Gruetter R (2009) Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. J Neurochem 111:368–379. doi:10.1111/j.1471-4159.2009.06349.x
El Idrissi A (2008a) Taurine increases mitochondrial buffering of calcium: role in neuroprotection. Amino Acids 34:321–328. doi:10.1007/s00726-006-0396-9
El Idrissi A (2008b) Taurine improves learning and retention in aged mice. Neurosci Lett 436:19–22. doi:10.1016/j.neulet.2008.02.070
El Idrissi A, Boukarrou L, Heany W et al (2009) Effects of taurine on anxiety-like and locomotor behavior of mice. Adv Exp Med Biol 643:207–215
Esposito K (2002) Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106:2067–2072. doi:10.1161/01.CIR.0000034509.14906.AE
Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222:236–245
Franconi F, Bennardini F, Mattana A et al (1995) Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Am J Clin Nutr 61:1115–1119
Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070. doi:10.1161/CIRCRESAHA.110.223545
Giribabu N, Srinivasarao N, Swapna Rekha S et al (2014) Centella asiatica attenuates diabetes induced hippocampal changes in experimental diabetic rats. Evid Based Complement Altern Med 2014:1–10. doi:10.1155/2014/592062
Gispen WH, Biessels GJ (2000) Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 23:542–549
Goodman HO, Shihabi ZK (1990) Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides. Biochem Med Metab Biol 43:1–9
Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Oxford University Press, Oxford
Hartmann A, Agurell E, Beevers C et al (2003) Recommendations for conducting the in vivo alkaline Comet assay. 4th International Comet Assay Workshop. Mutagenesis 18:45–51
Jia F, Yue M, Chandra D et al (2008) Taurine is a potent activator of extrasynaptic GABA(A) receptors in the thalamus. J Neurosci Off J Soc Neurosci 28:106–115. doi:10.1523/JNEUROSCI.3996-07.2008
Joko T, Washizuka S, Sasayama D et al (2016) Patterns of hippocampal atrophy differ among Alzheimer’s disease, amnestic mild cognitive impairment, and late-life depression. Psychogeriatr Off J Jpn Psychogeriatr Soc 16:355–361. doi:10.1111/psyg.12176
Jong CJ, Ito T, Mozaffari M et al (2010) Effect of β-alanine treatment on mitochondrial taurine level and 5-taurinomethyluridine content. J Biomed Sci 17:S25. doi:10.1186/1423-0127-17-S1-S25
Jong CJ, Azuma J, Schaffer S (2012) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42:2223–2232. doi:10.1007/s00726-011-0962-7
Ko S-H, Choi S-W, Ye S-K et al (2005) Comparison of the antioxidant activities of nine different fruits in human plasma. J Med Food 8:41–46. doi:10.1089/jmf.2005.8.41
L’Amoreaux WJ, Marsillo A, El Idrissi A (2010) Pharmacological characterization of GABAA receptors in taurine-fed mice. J Biomed Sci 17:S14. doi:10.1186/1423-0127-17-S1-S14
Lambert IH, Kristensen DM, Holm JB, Mortensen OH (2015) Physiological role of taurine–from organism to organelle. Acta Physiol Oxf Engl 213:191–212. doi:10.1111/apha.12365
Lee SC, Chan JCN (2015) Evidence for DNA damage as a biological link between diabetes and cancer. Chin Med J (Engl) 128:1543–1548. doi:10.4103/0366-6999.157693
Leszek J, Barreto GE, Gąsiorowski K et al (2016) Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system. CNS Neurol Disord: Drug Targets 15:329–336
Liu X, Mo Y, Gong J et al (2015) Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. Metab Brain Dis. doi:10.1007/s11011-015-9779-5
Magariños AM, McEwen BS (2000) Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci U S A 97:11056–11061
Malkov A, Ivanov AI, Popova I et al (2014) Reactive oxygen species initiate a metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 34:1540–1549. doi:10.1038/jcbfm.2014.121
Mezzomo NJ, Silveira A, Giuliani GS et al (2016) The role of taurine on anxiety-like behaviors in zebrafish: a comparative study using the novel tank and the light-dark tasks. Neurosci Lett 613:19–24. doi:10.1016/j.neulet.2015.12.037
Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175
Nadin SB, Vargas-Roig LM, Ciocca DR (2001) A silver staining method for single-cell gel assay. J Histochem Cytochem Off J Histochem Soc 49:1183–1186
Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790. doi:10.1038/35008121
Oliveira MWS, Minotto JB, de Oliveira MR et al (2010) Scavenging and antioxidant potential of physiological taurine concentrations against different reactive oxygen/nitrogen species. Pharmacol Rep PR 62:185–193
Pamidi N, Satheesha Nayak BN (2012) Effect of streptozotocin induced diabetes on rat hippocampus. Bratisl Lekárske Listy 113:583–588
Patel M (2016) Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 37:768–778. doi:10.1016/j.tips.2016.06.007
Rajendran P, Nandakumar N, Rengarajan T et al (2014) Antioxidants and human diseases. Clin Chim Acta 436:332–347. doi:10.1016/j.cca.2014.06.004
Reeta KH, Singh D, Gupta YK (2017) Chronic treatment with taurine after intracerebroventricular streptozotocin injection improves cognitive dysfunction in rats by modulating oxidative stress, cholinergic functions and neuroinflammation. Neurochem Int 108:146–156. doi:10.1016/j.neuint.2017.03.006
Rivas-Arancibia S, Guevara-Guzmán R, López-Vidal Y et al (2010) Oxidative stress caused by ozone exposure induces loss of brain repair in the hippocampus of adult rats. Toxicol Sci Off J Soc Toxicol 113:187–197. doi:10.1093/toxsci/kfp252
Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99. doi:10.1139/Y08-110
Toyoda A, Iio W (2013) Antidepressant-like effect of chronic taurine administration and its hippocampal signal transduction in rats. Adv Exp Med Biol 775:29–43. doi:10.1007/978-1-4614-6130-2_3
Trachtman H, Futterweit S, Sturman JA (1992) Cerebral taurine transport is increased during streptozocin-induced diabetes in rats. Diabetes 41:1130–1140
Tsounapi P, Saito M, Dimitriadis F et al (2012) Antioxidant treatment with edaravone or taurine ameliorates diabetes-induced testicular dysfunction in the rat. Mol Cell Biochem 369:195–204. doi:10.1007/s11010-012-1382-z
Uliasz TF, Hewett SJ (2000) A microtiter trypan blue absorbance assay for the quantitative determination of excitotoxic neuronal injury in cell culture. J Neurosci Methods 100:157–163
Wang X, Michaelis EK (2010) Selective neuronal vulnerability to oxidative stress in the brain. Front Aging Neurosci. doi:10.3389/fnagi.2010.00012
Yamagishi S, Matsui T (2010) Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev 3:101–108. doi:10.4161/oxim.3.2.11148
Zhang H, Huang M, Gao L, Lei H (2015) Region-specific cerebral metabolic alterations in streptozotocin-induced type 1 diabetic rats: an in vivo proton magnetic resonance spectroscopy study. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 35:1738–1745. doi:10.1038/jcbfm.2015.111
Acknowledgements
We thank Solange Bandiera and Alana W Hansen for their technical support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) and Pró-Reitoria de Pesquisa, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All applicable international, national, and or institutional guidelines for the care and use of animals were followed.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Caletti, G., Herrmann, A.P., Pulcinelli, R.R. et al. Taurine counteracts the neurotoxic effects of streptozotocin-induced diabetes in rats. Amino Acids 50, 95–104 (2018). https://doi.org/10.1007/s00726-017-2495-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-017-2495-1