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Evaluation of the Actions of Metformin and Taurine, Singly and in Combination, on Metabolic and Oxidative Alterations Caused by Diabetes in Rat Erythrocytes and Plasma

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Taurine 9

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 803))

Abstract

This study has compared the actions of metformin (MET) and taurine (TAU), singly and in combination, on diabetes-induced metabolic and oxidative alterations in a chemical rat model of diabetes. Groups of six male Sprague-Dawley rats, 225–250 g, were used in the study. Diabetes was induced on day 1 with streptozotocin, 60 mg/kg, i.p. The rats were then separately treated with MET, TAU or MET plus TAU, each at a 2.4 mM/kg/day p.o., or with insulin, 4 U/kg/day s.c., from day 15 to day 56. Blood samples were collected on day 57. One portion was assayed for HbA1c and the other was used to obtain plasma and red blood cells (RBCs). The plasma was used to measure glucose, insulin, and hemoglobin levels, and indices of oxidative stress; and the RBCs were analyzed for hemoglobin content, membrane ratio of cholesterol to phospholipids, and indices of oxidative stress. In comparison to normal rats, diabetic ones showed a marked increase in plasma glucose and blood HbA1c level, a lower plasma insulin, and evidence of significant hemolysis. In addition, oxidative stress was detected in the plasma and RBCs, and the RBC membrane ratio of cholesterol to phospholipids was higher in diabetic than in normal specimens. MET was more effective than TAU in attenuating the changes in circulating glucose, insulin and HbA1c levels, about equipotent in lowering changes in RBC membrane lipids and in preserving the RBC redox status, and weaker in attenuating changes in indices of oxidative stress. When used together, TAU was found to enhance the antioxidant actions of MET both in the plasma and RBCs. The present results suggest that MET and TAU are more protective against diabetes-induced metabolic and oxidative alterations when used together than separately, probably because of complementary actions.

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Abbreviations

CAT:

Catalase

GPx:

Glutathione peroxidase

GSH:

Reduced glutathione

GSSG:

Glutathione disulfide

HbA1c :

Glycated hemoglobin

INS:

Insulin

MDA:

Malondialdehyde

MET:

Metformin

RBCs:

Erythrocytes

SOD:

Superoxide dismutase

STZ:

Streptozotocin

TAU:

Taurine

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(Suppl 1):S35

    Article  PubMed Central  PubMed  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Alhaider AA, Korashy HM, Sayed-Ahmed MM, Mobark M, Kfoury H, Mansour MA (2011) Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression. Chem Biol Interact 192:233–242

    Article  CAS  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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bonnefont-Rousselot D, Raji B, Walrand S, Gardès-Albert M, Jore D, Legrand A, Peynet J, Vasson MP (2003) An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress. Metabolism 52:586–589

    Article  CAS  PubMed  Google Scholar 

  • Brøns C, Spohr C, Storgaard H, Dyenberg 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 

  • Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Chakraborty A, Chowdhury S, Bhattacharyya M (2011) Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diabetes Res Clin Pract 93:56–62

    Article  CAS  PubMed  Google Scholar 

  • Choi SW, Benzie IF, Ma SW, Strain JJ, Hannigan BM (2008) Acute hypoglycemia and oxidative stress: direct cause and effect? Free Radic Biol Med 44:1217–1231

    Article  CAS  PubMed  Google Scholar 

  • Dave GS, Kalia K (2007) Hyperglycemia induced oxidative stress in type 1 and type 2 diabetic patients with and without nephropathy. Cell Mol Biol (Noisy -le-grand) 53:68–78

    CAS  Google Scholar 

  • Deng Y, Wang W, Yu P, Xi Z, Xu L, Li X, He N (2013) Comparison of taurine. GABA, Glu, and Asp as scavengers of malondialdehyde in vitro and in vivo. Nanoscale Res Lett 8:190

    Article  PubMed Central  PubMed  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  CAS  PubMed  Google Scholar 

  • Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long- term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986

    Article  Google Scholar 

  • di Wu Q, Wang JH, Fennessy F, Redmond HP, Bouchier-Hayes D (1999) Taurine prevents high-glucose induced human vascular endothelial cell apoptosis. Am J Physiol Cell Physiol 277:C1229–C1238

    CAS  Google Scholar 

  • Erejuwa OO (2012) Management of diabetes mellitus: could simultaneous targeting of hyperglycemia and oxidative stress be a better panacea? Int J Mol Sci 13:2965–2972

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ersöz G, Mithat K, Babül A, Gönül B (1994) The effect of taurine on blood glucose, tissue glycogen and serum C-peptide levels on glucocorticoid administered rats. Gazi Med J 1:1–5

    Google Scholar 

  • Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2003) Are oxidative stress-activatedsignaling pathways mediators of insulin resistance and β-cell dysfunction. Diabetes 52:1–8

    Article  CAS  PubMed  Google Scholar 

  • Ewis SA, Abdel-Rahman MS (1995) Effect of metformin on glutathione and magnesium in normal and streptozotocin-induced diabetic rats. J Appl Toxicol 15:387–390

    Article  CAS  PubMed  Google Scholar 

  • Folch JM, Lees M, Stanley GHS (1957) A simple method for isolation and purification of total lipids from animal tissue. J Biol Chem 226:497–509

    CAS  PubMed  Google Scholar 

  • Giacco F, Browlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Goodman HO, Shihabi ZK (1990) Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides. Biochem Med Metab Biol 43:1–9

    Article  CAS  PubMed  Google Scholar 

  • Grieco CR, Colberg SR, Somma GT, Thompson AG, Vinik AT (2013) Melatonin supplementation improves glycemic control while lowering oxidative stress in type 2 diabetes. Int J Diabetes Res 2:45–49

    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 

  • Günzler WA, Flohé L (1985) Glutathione peroxidase. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press, Boca Raton, FL, pp 285–290

    Google Scholar 

  • Hahn UK, Bender RC, Bayne CJ (2001) Killing of Schistosoma mansoni sporocysts by hemocytes from resistant Biomphalaria glabrata: role of reactive oxygen species. J Parasitol 2001:292–299

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Issabeagloo I, Taghizadiyeh M, Kermanizadeh P (2011) Hepatoprotective effect of taurine against oxidative stress due to methotrexate in rat. Am J Animal Vet Sci 6:187–192

    Article  CAS  Google Scholar 

  • Jakus V (2000) The role of free radicals, oxidative stress and antioxidant systems in diabetic vascular disease. Bratisl Lek Listy 101:541–551

    CAS  PubMed  Google Scholar 

  • Juhan-Vague I, Roul C, Rahmani-Jourdheil D, Mishal Z, Driss F et al (1986) Rapid modifications of biophysical and biochemical parameters of red blood cell membrane from insulin dependent diabetics after insulin administration. Klin Wochenschr 64:1046–1049

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Lampson WG, Kramer JH, Schaffer SW (1983) Potentiation of the actions of insulin by taurine. Can J Physiol Pharmacol 61:457–463

    Article  CAS  PubMed  Google Scholar 

  • Maritim AC, Sanders RA, Watkins JB 3rd (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Motawi TMJ, Abou-Seil MA, Bader AM, Mahmoud MO (2013) Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients. BMC Endocr Disord 13:32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nakaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M (2000) Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. Am J Clin Nutr 71:54–58

    CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Obrosova IG, Fathallah L, Stevens MJ (2001) Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy. Exp Neurobiol 172:211–221

    Article  CAS  Google Scholar 

  • Odetti P, Pesce C, Traverso N, Menini S, Pesce Maineri E et al (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  CAS  PubMed  Google Scholar 

  • Patriarca S, Furfaro AL, Domenicotti C, Odetti P, Cottalasso D et al (2006) Supplementation with N-acetylcysteine and taurine failed to restore glutathione content in liver of streptozotocin-induced diabetic rats but protected from oxidative stress. Biochim Biophys Acta Mol Basis Dis 1741:48–54

    Article  Google Scholar 

  • Sharma R, Premachandra BR (1991) Membrane-bound hemoglobin as a marker of oxidative injury in adult and neonatal red blood cells. Biochem Met Metab Biol 46:33–44

    Article  CAS  Google Scholar 

  • Pushpakiran G, Mahalakshmi K, Anurandha CV (2004) Protective effects of taurine on glutathione and glutathione-dependent enzymes in ethanol-fed rats. Pharmazie 2004:869–872

    Google Scholar 

  • Pytel E, Olszewska-Banaszczyk M, Koter-Michalak M, Broncel M (2013) Increased oxidative stress and decreased membrane fluidity in erythrocytes of CAD patients. Biochem Cell Biol 91:315–318

    Article  CAS  PubMed  Google Scholar 

  • Ramachandran RR, Saraswathy M (2014) Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity. Toxicol Res 3:350–358

    Article  CAS  Google Scholar 

  • Rashid K, Das J, Sil PC (2013) Taurine ameliorate alloxan induced oxidative stress and intrinsic apoptotic pathway in the hepatic tissue of diabetic rats. Food Chem Toxicol 51:317–329

    Article  CAS  PubMed  Google Scholar 

  • Saleh AAS (2012) Effects of taurine and/or ginseng and their mixture on lipid profile and some parameters indicative of myocardial status in streptozotocin-diabetic rats. J Basic Appl Zool 65:267–273

    Article  CAS  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  CAS  PubMed  Google Scholar 

  • Stanescu M, Zamfirescu G, Iordachescu D (2002) The effect of glucose and insulin upon human erythrocyte membrane ATPases. Rom J Biophys 12:117–128

    CAS  Google Scholar 

  • Stewart JUCM (1979) Colorimetric determination of phospholipids with ammonium ferrothiocyanate. Anal Biochem 104:10–14

    Article  Google Scholar 

  • Tabatabaie T, Floyd RA (1994) Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents. Arch Biochem Biophys 314:112–119

    Article  CAS  PubMed  Google Scholar 

  • Tadolini B, Pintus G, Pinna GG, Bennardini F, Franconi F (1995) Effect of taurine and hypotaurine on lipid peroxidation. Biochem Biophys Res Commun 213:820–826

    Article  CAS  PubMed  Google Scholar 

  • 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 526:97–104

    Article  CAS  PubMed  Google Scholar 

  • Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E et al (1995) Taurine ameliorates chronic streptozotocin-induced diabetic nephropathy in rats. Am J Physiol 1995 269(3 Pt 2):F429–F438

    CAS  Google Scholar 

  • Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J (2009) Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits. Biochmie 91:261–270

    Article  CAS  Google Scholar 

  • Winterbourn CC (1985) Free-radical production and oxidative reactions of hemoglobin. Environ Health Perspect 64:321–330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yanardag R, Ozsoy-Sacan O, Bolkent S, Orak H, Karabulut-Bulan O (2005) Protective effects of metformin treatment on the liver injury of streptozotocin- diabetic rats. Hum Exp Toxicol 24:129–135

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Kim AK (2009) Effect of taurine on antioxidant enzymes system in B16F10 melanoma cells. Adv Exp Med Biol 643:491–499

    Article  CAS  PubMed  Google Scholar 

  • Zatalia SR, Sanusi H (2013) The role of antioxidants in the pathophysiology, complications, and management of diabetes mellitus. Acta Med Indones 45:141–147

    PubMed  Google Scholar 

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Correspondence to Cesar A. Lau-Cam .

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Budhram, R., Pandya, K.G., Lau-Cam, C.A. (2015). Evaluation of the Actions of Metformin and Taurine, Singly and in Combination, on Metabolic and Oxidative Alterations Caused by Diabetes in Rat Erythrocytes and Plasma. In: Marcinkiewicz, J., Schaffer, S. (eds) Taurine 9. Advances in Experimental Medicine and Biology, vol 803. Springer, Cham. https://doi.org/10.1007/978-3-319-15126-7_21

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