Skip to main content
SpringerLink
Log in

Comparative Evaluation of Taurine and Thiotaurine as Protectants Against Diabetes-Induced Nephropathy in a Rat Model

  • Conference paper
  • First Online:
Taurine 8

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 775))

Abstract

Taking into account the proven effectiveness of antioxidants in preventing experimentally induced diabetes in laboratory animals, this study was carried out with the specific purpose of comparing the effectiveness of two known antioxidants, the β-aminosulfonate taurine (TAU) and β-aminothiosulfonate thiotaurine (TTAU), in preventing biochemical, functional and histological alterations indicative of ­diabetic nephropathy. In the study, streptozotocin (60 mg/kg, orally) was used to induce type 2 diabetes mellitus in Sprague-Dawley rats. Starting on day 15 and continuing up to day 56, the rats received a daily single 2.4 mmol/kg oral dose of a sulfur-containing compound (TAU or TTAU) or 4 U/kg subcutaneous dose of isophane insulin (INS). Rats not receiving any treatment served as controls. After obtaining a 24 h urine sample, the animals were sacrificed by decapitation on day 57, and their blood and kidneys immediately collected. Diabetic rats exhibited marked hyperglycemia, hypoinsulinemia, hypoproteinemia, hyponatremia, hyperkalemia, azotemia, hypercreatinemia, increased plasma TGF β1, lipid peroxidation, plasma and kidney nitrite, and urine output; decreased glutathione redox status in plasma and kidney, decreased urine Na+ and K+, proteinuria and hypocreatinuria. Without exceptions, all the treatment compounds were found to markedly and variously attenuate these changes. Confirmation of protection by INS, TAU and TTAU was provided by the results of histological examination of kidney sections and which showed a more normal appearance than sections from diabetic animals. In most instances protection by TTAU was about equal to that by INS but greater than that by TAU.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

TAU:

Taurine

TTAU:

Thiotaurine

STZ:

Streptozotocin

GLC:

Glucose

INS:

Insulin

HbA1c :

Glycosylated hemoglobin

TGF-β1:

Transforming growth factor-β1

BUN:

Blood urea nitrogen

CRN:

Creatinine

K+ :

Potassium

Na+ :

Sodium

TP:

Total protein

MDA:

Malondialdehyde

GSH:

Reduced glutathione

GSSG:

Glutathione disulfide

References

  • 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:S35

    Article  PubMed  Google Scholar 

  • Adler S (2004) Diabetic nephropathy: linking histology, cell biology, and genetics. Kidney Int 66:2095–2106

    Article  PubMed  Google Scholar 

  • Aruoma OI, Halliwell B, Hoey BM, Butler J (1988) The antioxidant action of taurine, hypotaurine and their metabolic precursors. Biochem J 256:251–255

    PubMed  CAS  Google Scholar 

  • Arya A, Aggarwal S, Yadav HN (2010) Pathogenesis of diabetic nephropathy. Exp Clin Endocrinol Diabetes 2:24–29

    CAS  Google Scholar 

  • Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, Singh M (2008) Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst 9:189–195

    Article  PubMed  CAS  Google Scholar 

  • Balkan J, Doğru-Abbasoğlu S, Kanbağli O, Cevikbaş U, Aykaç-Toker G, Uysal M (2001) Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress. Hum Exp Toxicol 20:251–254

    Article  PubMed  CAS  Google Scholar 

  • Björck S, Nyberg G, Mulec H, Granerus G, Herlitz H, Aurell M (1986) Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. Br Med J (Clin Res Ed) 293:471–474

    Article  Google Scholar 

  • 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 58:1239–1247

    Article  PubMed  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  PubMed  CAS  Google Scholar 

  • Catherwood MA, Powell LA, Anderson P, McMaster D, Sharpe PC, Trimble ER (2002) Glucose-induced oxidative stress in mesangial cells. Kidney Int 61:599–608

    Article  PubMed  CAS  Google Scholar 

  • Cavallini D, De Marco C, Mondovi B (1960) Enzymatic conversion of cystamine into thiotaurine. Boll Soc Ital Biol Sper 36:1915–1918

    PubMed  CAS  Google Scholar 

  • Cavallinid D, De Marco C, Mondovi B (1959) Chromatographic evidence on the occurrence of thiotaurine in the urine of rats fed with cystine. Biol Chem 234:854–857

    Google Scholar 

  • Craven PA, DeRubertis FR, Kagan VE, Melhem M, Studer RK (1997) Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes. J Am Soc Nephrol 8:1405–1414

    PubMed  CAS  Google Scholar 

  • Das J, Sil PC (2012) Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino Acids 43:1509–1523

    Google Scholar 

  • Derlacz RA, Sliwinska M, Piekutowska A, Winiarska K, Drozak J, Bryla J (2007) Melatonin is more effective than taurine and 5-hydroxytryptophan against hyperglycemia-induced kidney-cortex tubules injury. J Pineal Res 42:203–209

    Article  PubMed  CAS  Google Scholar 

  • Doerr RC, Fox JB, Lakritz L, Fiddler W (1981) Determination of nitrite in cured meats by chemiluminescence. Anal Chem 53:381–384

    Article  CAS  Google Scholar 

  • Egawa M, Kohno Y, Kumano Y (1999) Oxidative effects of cigarette smoke on the human skin. Int J Cosmet Sci 21:83–98

    Article  PubMed  CAS  Google Scholar 

  • Fares J, Kanaan M, Chaaya M, Azar S (2010) Fluctuations in glycosylated hemoglobin (HbA1c) as a predictor for the development of diabetic nephropathy in type 1 diabetic patients. Int J Diabetes Mellitus 2:10–14

    Article  Google Scholar 

  • Fellman JH, Green TR, Eicher AL (1987) The oxidation of hypotaurine to taurine: bis-aminoethyl-α-disulfone, a metabolic intermediate in mammalian tissue. Adv Exp Med Biol 217:39–48

    PubMed  CAS  Google Scholar 

  • Flyvbjerg A (2000) Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease. Diabetologia 43:1205–1223

    Article  PubMed  CAS  Google Scholar 

  • Flyvbjerg A, Dagnaes-Hansen F, De Vriese AS, Schrijvers BF, Tilton RG, Rasch R (2002) Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody. Diabetes 51:3090–3094

    Article  PubMed  CAS  Google Scholar 

  • Franconi F, Di Leo MA, Bennardini F, Ghirlanda G (2004) Is taurine beneficial in reducing risk factors of diabetes? Neurochem Res 29:143–150

    Article  PubMed  CAS  Google Scholar 

  • Goldfarb S, Ziyadeh FN (2001) TGF-β: a crucial component of the pathogenesis of diabetic nephropathy. Trans Am Clin Climatol Assoc 112:27–33

    PubMed  CAS  Google Scholar 

  • Green TR, Fellman JH, Eicher AL, Pratt KL (1991) Antioxidant role and subcellular location of hypotaurine and taurine in human neutrophils. Biochim Biophys Acta 1073:91–97

    Article  PubMed  CAS  Google Scholar 

  • Güntherberg H, Rost J (1966) The true oxidized glutathione content of red blood cells obtained by new enzymic and paper chromatographic methods. Anal Biochem 15:205–210

    Article  PubMed  Google Scholar 

  • Ha H, Kim KH (1999) Pathogenesis of diabetic nephropathy: the role of oxidative stress and kinase C. Diabetes Res Clin Pract 45:147–151

    Article  PubMed  CAS  Google Scholar 

  • Ha H, Lee HB (2000) Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose. Kidney Int 58(Suppl 77):S-19–S-25

    Google Scholar 

  • Ha H, Yu MR, Choi YJ, Lee HB (2001) Activation of protein kinase C-δ and C-ε by oxidative stress in early diabetic rat kidney. Am J Kidney Dis 38:S204–S207

    Article  PubMed  CAS  Google Scholar 

  • Ha H, Yu MR, Kim KH (1999) Melatonin and taurine reduce early glomerulopathy in diabetic rats. Free Radic Biol Med 26:944–950

    Article  PubMed  CAS  Google Scholar 

  • Haber CA, Lam TK, Yu Z, Gupta N, Goh T, Bogdanovic E, Giacca A, Fantus IG (2003) N-Acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. Am J Physiol Endocrinol Metab 285:E744–E753

    PubMed  CAS  Google Scholar 

  • Hansen SH (2001) The role of taurine in diabetes and the development of diabetic complications. Diabetes Metab Res Rev 17:330–346

    Article  PubMed  CAS  Google Scholar 

  • Hebden RA, Gardiner SM, Bennett T, MacDonald IA (1986) The influence of streptozotocin-induced diabetes mellitus on fluid and electrolyte handling in rats. Clin Sci (Lond) 70:111–117

    CAS  Google Scholar 

  • Higo S, Miyata S, Jiang QY, Kitazawa R, Kitazawa S, Kasuga M (2008) Taurine administration after appearance of proteinuria retards progression of diabetic nephropathy in rats. Kobe J Med Sci 54:E35–E45

    PubMed  Google Scholar 

  • Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226

    Article  PubMed  CAS  Google Scholar 

  • Huang JS, Chuang LY, Guh JY, Huang YJ, Hsu MS (2007) Antioxidants attenuate high glucose-induced hypertrophic growth in renal tubular epithelial cells. Am J Physiol 293:F1072–F1082

    Article  CAS  Google Scholar 

  • Huang JS, Chuang LY, Guh JY, Yang YL, Hsu MS (2008) Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells. Toxicol Appl Pharmacol 233:220–226

    Article  PubMed  CAS  Google Scholar 

  • Jiang QY (2002) Mechanisms of beneficial effects of taurine on diabetic nephropathy. Med J Kobe Univ 62:119–126

    CAS  Google Scholar 

  • Joyner JL, Peyer SM, Lee RW (2003) Possible roles of sulfur-containing amino acids in a chemoautotrophic bacterium-mollusc symbiosis. Biol Bull 205:331–338

    Article  PubMed  CAS  Google Scholar 

  • Kaplan B, Karabay G, Zağyapan RD, Ozer C, Sayan H, Duyar I (2004) Effects of taurine in glucose and taurine administration. Amino Acids 27:327–333

    Article  PubMed  CAS  Google Scholar 

  • Kashihara N, Haruna Y, Kondeti VK, Kanwar YS (2010) Oxidative stress in diabetic nephropathy. Curr Med Chem 17:4256–4269

    Article  PubMed  CAS  Google Scholar 

  • Katsumata M, Kiuchi K, Tashiro T, Uchikuga S (1997) Methods for scavenging active oxygen compounds and preventing damage from ultra violet B rays using taurine analogues. US Patent Number 5:601,806

    Google Scholar 

  • Kono Y (1998) New raw materials and new technologies for cosmetics. (Part I). Development and its application of “sebum antioxidant thiotaurine” for cosmetics. Fragr J 26:9–14

    Google Scholar 

  • Kono Y, Miyaji Y (2000) Peroxidation in the skin and its prevention. Jpn J Inflamm 20:119–129

    Google Scholar 

  • Koya D, Hayashi K, Kitada M, Kashiwagi A, Kikkawa R, Haneda M (2003) Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats. J Am Soc Nephrol 14:S250–S253

    Article  PubMed  CAS  Google Scholar 

  • Kulakowski EC, Maturo J (1984) Hypoglycemic properties of taurine: not mediated by enhanced insulin release. Biochem Pharmacol 33:2835–2838

    Article  PubMed  CAS  Google Scholar 

  • Lee EA, Seo JY, Jiang Z, Yu MR, Kwon MK, Ha H, Lee HB (2005) Reactive oxygen species mediate high glucose-induced plasminogen activator inhibitor-1 up-regulation in mesangial cells and in diabetic kidney. Kidney Int 67:1762–1771

    Article  PubMed  CAS  Google Scholar 

  • Lee HB, Yu MR, Yang Y, Jiang Z, Ha H (2003) Reactive oxygen species-regulated signaling ­pathways in diabetic nephropathy. J Am Soc Nephrol 14:S241–S245

    Article  PubMed  CAS  Google Scholar 

  • Li F, Obrosova IG, Abatan O, Tian D, Larkin D, Stuenkel EL, Stevens MJ (2004) Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats. Am J Physiol Endocrinol Metab 288:E29–E36

    Article  Google Scholar 

  • Mathiesen ER, Hommel E, Giese J, Parving HH (1991) Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria. Br Med J 303:81–87

    Article  CAS  Google Scholar 

  • Miller JA (1999) Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus. J Am Soc Nephrol 10:1778–1785

    PubMed  CAS  Google Scholar 

  • Monnier L, Colette C (2008) Fasting glucose and postprandial glycemia: which is the best target for improving outcomes? The Apollo and 4-T Trials. Expert Opin Pharmacother 9:2857–2865

    Article  PubMed  CAS  Google Scholar 

  • Naito Y, Uchiyama K, Aoi W, Hasegawa G, Nakamura N, Yoshida N, Maoka T, Takahashi J, Yoshikawa T (2004) Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. Biofactors 20:49–59

    Article  PubMed  CAS  Google Scholar 

  • Nandhini AT, Thirunavukkarasu V, Anuradha CV (2004) Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine. Acta Physiol Scand 181:297–303

    Article  PubMed  CAS  Google Scholar 

  • Obrosova IG (2005) Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications. Antioxid Redox Signal 7:1543–1552

    Article  PubMed  CAS  Google Scholar 

  • Obrosova IG, Stevens MJ (1999) Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens. Invest Ophthalmol Vis Sci 40:680–688

    PubMed  CAS  Google Scholar 

  • Odetti P, Pesce C, Traverso N, Menini S, Maineri EP, Cosso L, Valentini S, Patriarca S, Cottalasso D, Marinari UM, Pronzato MA (2003) Comparative trial of N-acetyl-cysteine, taurine, and oxerutin on skin and kidney damage in long-term experimental diabetes. Diabetes 52:499–505

    Article  PubMed  CAS  Google Scholar 

  • Prabhakar S, Starnes J, Shi S, Lonis B, Tran R (2007) Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production. J Am Soc Nephrol 18:2945–2952

    Article  PubMed  CAS  Google Scholar 

  • Pruski AM, Fiala-Médioni A (2003) Stimulatory effect of sulphide on thiotaurine synthesis in three hydrothermal-vent species from the East Pacific Rise. J Exp Biol 206:2923–2930

    Article  PubMed  CAS  Google Scholar 

  • Reckelhoff JF, Tygart VL, Mitias MM, Walcott JL (1993) STZ-induced diabetes results in decreased activity of glomerular cathepsin and metalloprotease in rats. Diabetes 42:1425–1432

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro RA, Bonfleur ML, Amaral AG, Vanzela EC, Rocco SA, Boschero AC, Carneiro EM (2009) Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets. Diabetes Metab Res Rev 25:370–379

    Article  PubMed  CAS  Google Scholar 

  • Rossing K, Christensen PK, Jensen BR, Parving HH (2002a) Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. Diabetes Care 25:95–100

    Article  PubMed  CAS  Google Scholar 

  • Rossing P, Hougaard P, Parving HH (2002b) Risk factors for development of incipient and diabetic nephropathy in type 1 diabetic patients: a 10-year prospective observational study. Diabetes Care 25:859–864

    Article  PubMed  Google Scholar 

  • Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99

    Article  PubMed  CAS  Google Scholar 

  • Simşek M, Naziroğlu M, Erdinç A (2005) Moderate exercise with a dietary vitamin C and E combination protects against streptozotocin-induced oxidative damage to the kidney and lens in pregnant rats. Exp Clin Endocrinol Diabetes 113:53–59

    Article  PubMed  Google Scholar 

  • Tada H, Ishii H, Isogai S (1997) Protective effect of D-alpha-tocopherol on the function of human mesangial cells exposed to high glucose concentrations. Metabolism 46:779–784

    Article  PubMed  CAS  Google Scholar 

  • Trachtman H, Futterweit S, Bienkowski R (1993) Taurine prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells. Biochem Biophys Res Commun 191:759–765

    Article  PubMed  CAS  Google Scholar 

  • Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS, Sturman JA, Boles TH (1995) Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. Am J Physiol 269:F429–F438

    PubMed  CAS  Google Scholar 

  • Trachtman H, Futterweit S, Prenner J, Hanon S (1994) Antioxidants reverse the antiproliferative effect of high glucose and advanced glycosylation end products in cultured rat mesangial cells. Biochem Biophys Res Commun 199:346–352

    Article  PubMed  CAS  Google Scholar 

  • Vaishya R, Singh J, Lal H (2009) Biochemical effects of irbesartan in experimental diabetic nephropathy. Indian J Pharmacol 41:252–254

    Article  PubMed  CAS  Google Scholar 

  • Verzola D, Bertolotto MB, Villaggio B, Ottonello L, Dallegri F, Frumento G, Berruti V, Gandolfo MT, Garibotto G, Deferran G (2002) Taurine prevents apoptosis induced by high ambient glucose in human tubule renal cells. J Investig Med 50:443–451

    Article  PubMed  CAS  Google Scholar 

  • Wang LJ, Zhang L, Yu Y, Wang Y, Niu N (2008) The protective effects of taurine against early renal injury in STZ-induced diabetic rats, correlated with inhibition of renal LOX-1-mediated ICAM-1 expression. Ren Fail 30:763–771

    Article  PubMed  CAS  Google Scholar 

  • Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J (2008) Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits. Biochimie 91:261–270

    Article  PubMed  Google Scholar 

  • Wollenberger A, Ristau O, Schoffa G (1960) Eine einfache Technik der extrem schneller Abkühlung grösserer Gewebstücke. Pflügers Arch. Gesamte Physiol. Menschen Tiere 270:399–412

    Article  PubMed  CAS  Google Scholar 

  • Yancey PH (2005) Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol 208:2819–2830

    Article  PubMed  CAS  Google Scholar 

  • Yancey PH, Ishikawa J, Meyer B, Girguis PR, Lee RW (2009) Thiotaurine and hypotaurine contents in hydrothermal-vent polychaetes without thiotrophic endosymbionts: correlation with sulfide exposure. J Exp Zool A Ecol Genet Physiol 311A:439–447

    Article  CAS  Google Scholar 

  • Yao HT, Lin P, Chang YW, Chen CT, Chiang MT, Chang L, Kuo YC, Tsai HT, Yeh TK (2009) Effect of taurine supplementation on cytochrome P450 2E1 and oxidative stress in the liver and kidneys of rats with streptozotocin-induced diabetes. Food Chem Toxicol 47:1703–1709

    Article  PubMed  CAS  Google Scholar 

  • Yoshiyuki K, Yoshiki M (2000) Peroxidation in the skin and its prevention. Jpn J Inflamm 20:119–129

    Article  PubMed  CAS  Google Scholar 

  • Zheng CM, Ma WY, Wu CC, Lu KC (2012) Glycated albumin in diabetic patients with chronic kidney disease. Clin Chim Acta 413:1555–1561

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. John’s University, College of Pharmacy and Health Professions, Jamaica, New York, NY, 11439, USA

    Kashyap G. Pandya, Roshil Budhram, George Clark & Cesar A. Lau-Cam

Authors
  1. Kashyap G. Pandya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roshil Budhram
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cesar A. Lau-Cam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cesar A. Lau-Cam .

Editor information

Editors and Affiliations

  1. City University of New York, Center for Developmental Neuroscience, College of Staten Island, 2800 Victory Blvd, Staten Island, 10314, New York, USA

    Abdeslem El Idrissi

  2. City University of New York, Department of Biology, College of Staten Island, Victory Blvd 2800, Staten Island, 10314, New York, USA

    William J. L'Amoreaux

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this paper

Cite this paper

Pandya, K.G., Budhram, R., Clark, G., Lau-Cam, C.A. (2013). Comparative Evaluation of Taurine and Thiotaurine as Protectants Against Diabetes-Induced Nephropathy in a Rat Model. In: El Idrissi, A., L'Amoreaux, W. (eds) Taurine 8. Advances in Experimental Medicine and Biology, vol 775. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6130-2_29

Download citation

Publish with us

Policies and ethics

Search

Navigation