Taurine 8 pp 321-343 | Cite as

Protection by Taurine and Thiotaurine Against Biochemical and Cellular Alterations Induced by Diabetes in a Rat Model

  • Roshil Budhram
  • Kashyap G. Pandya
  • Cesar A. Lau-CamEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 775)


In this study, the actions of taurine (TAU), a sulfonate, and thiotaurine (TTAU), a thiosulfonate, on diabetes-mediated biochemical alterations in red blood cells (RBCs) and plasma and on the RBC membrane, morphology and spectrin distribution were examined in rats. Diabetes was induced in male Sprague–Dawley rats with streptozotocin (60 mg/kg i.p.) and allowed to progress for 14 days. From days to 56, the rats received a daily, 2.4 mmol/kg, oral dose of TAU or TTAU, 2 mL oral dose of physiological saline or 4 U/kg subcutaneous dose of isophane insulin (INS). Naive rats served as the control group. The rats were sacrificed on day 57 and their blood was collected to measure HbA1c, to isolate intact RBCs, and to obtain plasma. A 6-weeks treatment with INS effectively lowered the elevations in plasma glucose, cholesterol, triglycerides, and plasma and RBC malondialdehyde and glutathione disulfide while effectively counteracting the decreases in plasma INS, plasma and RBC glutathione redox status, and plasma and RBC activities of antioxidant enzymes caused by diabetes. Also, INS returned the echynocytic appearance and peripheral location of spectrin seen in RBCs from diabetic rats to the normal discocytic shape and uniform distribution. TAU and TTAU were as effective as INS in inhibiting malondialdehyde formation, changes in redox status and oxidative stress in both the plasma and RBC, but were much less effective in controlling hyperglycemia and hypoinsulinemia. Furthermore TTAU was more effective than INS or TAU in lowering the increase in cholesterol to phospholipids ratio in the RBC membrane and, unlike TAU, it was able to normalize the RBC morphology and spectrin distribution.


Treatment Compound Glutathione Redox Status Mitochondrial Superoxide Anion Production Isophane Insulin Stanbio Laboratory 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.











Red blood cells




Glycated hemoglobin


Lipid peroxidation










Reduced glutathione


Glutathione disulfide




Glutathione peroxidase


Superoxide dismutase


  1. Acharya M, Lau-Cam CA (2010) Comparison of the protective actions of N-acetylcysteine, hypotaurine and taurine against acetaminophen-induced hepatotoxicity in the rat. J Biomed Sci 17:S35CrossRefPubMedGoogle Scholar
  2. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefPubMedGoogle Scholar
  3. Alciguzel Y, Ozen I, Aslan M, Karayalcin U (2003) Activities of xanthine oxidoreductase and antioxidant enzymes in different tissues of diabetic rats. J Lab Clin Med 142:172–177CrossRefGoogle Scholar
  4. Arora S, Ojha SK, Vohora D (2009) Characterisation of streptozotocin induced diabetes mellitus in Swiss albino mice. Global J Pharmacol 3:81–84Google Scholar
  5. Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9CrossRefPubMedGoogle Scholar
  6. Beard KM, Shangari N, Wu B, O’Brien PJ (2003) Metabolism, not autoxidation, plays a role in α-oxoaldehyde- and reducing sugar-induced erythrocyte GSH depletion: relevance for diabetes mellitus. Mol Cell Biochem 252:331–338CrossRefPubMedGoogle Scholar
  7. Bhor VM, Raghuram N, Sivakami S (2004) Oxidative damage and altered antioxidant enzyme activities in the small intestine of streptozotocin-induced diabetic rats. Int J Biochem Cell Biol 36:89–97CrossRefPubMedGoogle Scholar
  8. Brøns C, Spohr C, Storgaard H, Dyerberg J, Vaag A (2004) Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus. Eur J Clin Nutr 58:1239–1247CrossRefPubMedGoogle Scholar
  9. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMedGoogle Scholar
  10. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625CrossRefPubMedGoogle Scholar
  11. Ceriello A (2005) Postprandial hyperglycemia and diabetes complications: is it time to treat? Diabetes 54:1–7CrossRefPubMedGoogle Scholar
  12. Chauncey KB, Tenner TE Jr, Lombardini JB et al (2003) The effect of taurine supplementation on patients with type 2 diabetes mellitus. Adv Exp Med Biol 526:91–96CrossRefPubMedGoogle Scholar
  13. Cherif H, Reusens B, Ahn MT, Hoet JJ, Remacle C (1998) Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet. J Endocrinol 159:341–348CrossRefPubMedGoogle Scholar
  14. Costagliola C (1990) Oxidative state of glutathione in red blood cells and plasma of diabetic patients: in vivo and in vitro study. Clin Physiol Biochem 8:204–210PubMedGoogle Scholar
  15. Darmaun D, Smith SD, Sweeten S, Sager BK, Welch S, Mauras N (2005) Evidence for accelerated rates of glutathione utilization and glutathione depletion in adolescents with poorly controlled type 1 diabetes. Diabetes 54:190–196CrossRefPubMedGoogle Scholar
  16. Desco MC, Asensi N, Márquez R et al (2002) Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes 51:1118–1124CrossRefPubMedGoogle Scholar
  17. Desouky OS (2009) Rheological and electrical behavior of erythrocytes in patients with diabetes mellitus. Rom J Biophys 19:239–250Google Scholar
  18. Folch J, Lees M, Stanley GHS (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509PubMedGoogle Scholar
  19. Fujiwara Y, Kondo T, Murakami K, Kawakami Y (1989) Decrease of the inhibition of lipid peroxidation by glutathione-dependent system in erythrocytes of non-insulin dependent diabetics. J Mol Med 67:336–341Google Scholar
  20. Goodman HO, Shihabi ZK (1990) Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides. Biochem Med Metab Biol 43:1–9CrossRefPubMedGoogle Scholar
  21. Gossai D, Lau-Cam CA (2009) The effects of taurine, taurine homologs and hypotaurine on cell and membrane antioxidative system alterations caused by type 2 diabetes in rat erythrocytes. Adv Exp Med Biol 643:359–368CrossRefPubMedGoogle Scholar
  22. Günzler WA, Flohé L (1985) Glutathione peroxidase. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC, Boca Raton, FL, pp 285–290Google Scholar
  23. Guzik TJ, Mussa S, Gastaldi D et al (2002) Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105:1656–1662CrossRefPubMedGoogle Scholar
  24. Hisalkar PJ, Patne AB, Fawade MM (2012) Assessment of plasma antioxidant levels in type 2 diabetes patients. Int J Biol Med Res 3:1796–1800Google Scholar
  25. Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226CrossRefPubMedGoogle Scholar
  26. Jain SK (1984) The accumulation of malonyldialdehyde, a product of fatty acid peroxidation, can disturb aminophospholipid organization in the membrane bilayer of human erythrocytes. J Biol Chem 259:3391–3394PubMedGoogle Scholar
  27. Jain SK, Levine SN, Duetta J, Hollier B (1990) Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. Metabolism 39:971–975CrossRefPubMedGoogle Scholar
  28. Jain SK, McVie R, Duett J, Herbst JJ (1989) Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes 38:1539–1543CrossRefPubMedGoogle Scholar
  29. Jain SK, McVie R, Smith T (2000) Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children. Diabetes Care 23:1389–1394CrossRefPubMedGoogle Scholar
  30. Järvi AE, Karlström BE, Granfeldt YE et al (1999) Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients. Diabetes Care 22:10–18CrossRefPubMedGoogle Scholar
  31. Kalapos MP, Andrea Littauer A, de Groot H (1993) Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes. Arch Toxicol 67:369–372CrossRefPubMedGoogle Scholar
  32. Kędziora-Kornatowska KZ, Luciak M, Blaszczyk J, Pawlak W (1998) Lipid peroxidation and activities of antioxidant enzymes in erythrocytes of patients with non-insulin dependent diabetes with or without diabetic nephropathy. Nephrol Dial Transplant 13:2829–2832CrossRefPubMedGoogle Scholar
  33. Lee AY, Chiung SS (1999) Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 13:23–30PubMedGoogle Scholar
  34. Likidlilid A, Patchanans N, Peerapatdit T, Sriratanasathavorn C (2010) Lipid peroxidation and antioxidant enzyme activities in erythrocytes of type 2 diabetic patients. J Med Assoc Thai 93:682–693PubMedGoogle Scholar
  35. Loven D, Schedl H, Wilson H, Daabees TT et al (1986) Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozocin-induced diabetes. Diabetes 35:503–507CrossRefPubMedGoogle Scholar
  36. Maritim AC, Moore BH, Sanders RA, Watkins JB III (1999) Effects of melatonin on oxidative stress in streptozotocin-induced diabetic rats. Int J Toxicol 18:161–166CrossRefGoogle Scholar
  37. Maritim AC, Sanders RA, Watkins JB III (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38CrossRefPubMedGoogle Scholar
  38. Maturo J, Kulakowski EC (1988) Taurine binding to the purified insulin receptor. Biochem Pharmacol 37:3755–3760CrossRefPubMedGoogle Scholar
  39. Mayfield J (1998) Diagnosis and classification of diabetes mellitus: new criteria. Am Fam Physician 58:1355–1362PubMedGoogle Scholar
  40. 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 247:3170–3175PubMedGoogle Scholar
  41. Moller DE (2001) New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414(6865):821–827CrossRefPubMedGoogle Scholar
  42. Monnier L, Colette C (2008) Glycemic variability: should we and can we prevent it? Diabetes Care 31(suppl 2):S150–S154CrossRefPubMedGoogle Scholar
  43. Monnier L, Mas E, Ginet C et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. J Am Med Assoc 295:1681–1687CrossRefGoogle Scholar
  44. Murakami K, Takahito K, Ohtsuka Y et al (1989) Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism 38:753–758CrossRefPubMedGoogle Scholar
  45. Nandhini ATA, Thirunavukkarasu V, Anuradha CV (2004) Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine. Acta Physiol Scand 181:297–303CrossRefPubMedGoogle Scholar
  46. Nishikawa T, Edelstein D, Brownlee M (2000) The missing link: a single unifying mechanism for diabetic complications. Kidney Int 58:S26–S30CrossRefGoogle Scholar
  47. Obrosova IG, Stavniichuk R, Drel VR (2010) Different roles of 12/15-lipoxygenase in diabetic large and small fiber peripheral and autonomic neuropathies. Am J Pathol 177:1436–1447CrossRefPubMedGoogle Scholar
  48. Oprescu AI, Bikopoulos G, Naassan A et al (2007) Fatty acid–induced reduction in ­glucose-stimulated insulin secretion: evidence for a role of oxidative stress in vitro and in vivo. Diabetes 56:2927–2937CrossRefPubMedGoogle Scholar
  49. Peuchant E, Delmas-Beauvieux MC, Couchouron A et al (1997) Short-term insulin therapy and normoglycemia. Effects on erythrocyte lipid peroxidation in NIDDM patients. Diabetes Care 20:202–207CrossRefPubMedGoogle Scholar
  50. Pieczenik SR, Neustadt J (2007) Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol 83:84–92CrossRefPubMedGoogle Scholar
  51. Rahimi R, Nikfar S, Larijani B, Abdollahi M (2005) A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 59:365–373CrossRefPubMedGoogle Scholar
  52. Ricci C, Pastukh V, Leonard J et al (2008) Mitochondrial DNA damage triggers mitochondrial superoxide generation and apoptosis. Am J Physiol Cell Physiol 294:C413–C422CrossRefPubMedGoogle Scholar
  53. Samiec P, Drews-Botsch C, Flagg EF et al (1998) Glutathione in human plasma: decline in association with ageing, age-related macular degeneration and diabetes. Free Radic Biol Med 24:699–704CrossRefPubMedGoogle Scholar
  54. Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99CrossRefPubMedGoogle Scholar
  55. Sekhar RV, McKay SV, Patel SG et al (2010) Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care 34:164–167Google Scholar
  56. Sharma R, Premachandra BR (1991) Membrane-bound hemoglobin as a marker of oxidative injury in adult and neonatal red blood cells. Biochem Med Metab Biol 46:33–44CrossRefPubMedGoogle Scholar
  57. Stewart JCM (1979) Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem 104:10–14CrossRefGoogle Scholar
  58. Straface E, Rivabene R, Masella R et al (2002) Structural changes of the erythrocyte as a marker of non-insulin-dependent diabetes: protective effects of N-acetylcysteine. Biochem Biophys Res Commun 290:1393–1398CrossRefPubMedGoogle Scholar
  59. Sundaram RK, Bhaskar A, Vijayalingam S et al (1996) Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications. Clin Sci 90:255–260PubMedGoogle Scholar
  60. Tenner TE Jr, Zhang XJ, Lombardini JB (2003) Hypoglycemic effects of taurine in the alloxan-treated rabbit: a model for type 1 diabetes. Adv Exp Med Biol 526:97–104CrossRefPubMedGoogle Scholar
  61. Tokunaga H, Yoneda Y, Kuriyama K (1979) Protective actions of taurine against streptozotocin-induced hyperglycemia. Biochem Pharmacol 28:2807–2811CrossRefPubMedGoogle Scholar
  62. Tourrel C, Bailbe D, Lacorne M, Meile MJ, Kergoat M, Portha B (2002) Persistent improvement of type 2 diabetes in the Goto–Kakizaki rat model by expansion of the β-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4. Diabetes 51:1443–1452CrossRefPubMedGoogle Scholar
  63. Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS, Sturman JA, Boles TH (1995) Taurine ameliorates chronic streptozotocin-induced diabetic nephropathy in rats. Am J Physiol 269:F429–F438CrossRefPubMedGoogle Scholar
  64. Trocino RA, Akazawa S, Ishibashi M et al (1995) Significance of glutathione depletion and oxidative stress in early embryogenesis in glucose-induced rat embryo culture. Diabetes 44: 992–998CrossRefPubMedGoogle Scholar
  65. Valko M, Leibfritz D, Moncola J et al (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84CrossRefPubMedGoogle Scholar
  66. Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J (2009) Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits. Biochimie 91:261–270CrossRefPubMedGoogle Scholar
  67. Wohaieb SA, Godin DV (1987) Alterations in free radical tissue-defense mechanisms in streptozotocin-induced diabetes in rat. Effects of insulin treatment. Diabetes 36:1014–1018CrossRefPubMedGoogle Scholar
  68. Ziparo E, Lemay A, Marchesi VT (1978) The distribution of spectrin along the membranes of normal and echinocytic human erythrocytes. J Cell Sci 34:91–101CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Roshil Budhram
    • 1
  • Kashyap G. Pandya
    • 1
  • Cesar A. Lau-Cam
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health ProfessionsSt. John’s University, JamaicaNew YorkUSA

Personalised recommendations