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Diabetologia

Erschienen in:

01.07.2010 | Article

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

verfasst von: N. Karachalias, R. Babaei-Jadidi, N. Rabbani, P. J. Thornalley

Erschienen in: Diabetologia | Ausgabe 7/2010

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Abstract

Aims/hypothesis

The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy.

Methods

Diabetes was induced in male Sprague–Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg⁻¹ day⁻¹) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS.

Results

There were two- to fourfold increases in fructosyl-lysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven- to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy.

Conclusions/interpretation

AGEs, particularly arginine-derived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

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Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG (2006) Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int 69:2057–2063CrossRefPubMed

Thornalley PJ (2005) The potential role of thiamine (vitamin B1) in diabetic complications. Curr Diabetes Res 1:287–298CrossRef

Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley PJ (2003) Prevention of incipient diabetic nephropathy by high dose thiamine and benfotiamine. Diabetes 52:2110–2120CrossRefPubMed

Hammes H-P, Du X, Edelstein D et al (2003) Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 9:294–299CrossRefPubMed

Stracke H, Hammes HP, Werkmann D et al (2001) Efficacy of benfotiamine vs thiamine on function and glycation products of peripheral nerves in diabetic rats. Exp Clin Endocrinol Diabetes 109:330–336CrossRefPubMed

Rabbani N, Shahzad Alam S, Riaz S et al (2008) High dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a pilot randomised, double-blind, placebo-controlled study. Diabetologia 52:208–212CrossRefPubMed

Rabbani N, Alam S, Riaz S et al (2009) Thiamine in diabetic nephropathy: a novel treatment modality? Reply to Alkhalaf A, Kleefstra N, Groenier KH et al [letter]. Diabetologia 52:1214–1216CrossRef

Thornalley PJ (2006) Quantitative screening of protein glycation, oxidation, and nitration adducts by LC–MS/MS: protein damage in diabetes, uremia, cirrhosis, and Alzheimer's disease. In: Dalle-Donne I, Scaloni A, Butterfield DA (eds) Redox proteomics. Wiley, Hoboken, pp 681–728CrossRef

Babaei-Jadidi R, Karachalias N, Kupich C, Ahmed N, Thornalley PJ (2004) High dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia 47:2235–2246CrossRefPubMed

10.

Winkler BS (1972) The electroretinogram of the isolated rat retina. Vision Res 12:1183–1198CrossRefPubMed

11.

Ahmed N, Argirov OK, Minhas HS, Cordeiro CA, Thornalley PJ (2002) Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic assay with derivatisation by aminoquinolyl-N-hydroxysuccimidyl-carbamate and application to Ne-carboxymethyl-lysine- and Ne-(1-carboxyethyl)lysine-modified albumin. Biochem J 364:1–14PubMed

12.

Thornalley PJ, Battah S, Ahmed N et al (2003) Quantitative screening of advanced glycation endproducts in cellular and extracellular proteins by tandem mass spectrometry. Biochem J 375:581–592CrossRefPubMed

13.

Soulis-Liparota T, Cooper M, Papazoglou DX, Clarke B, Jerums G (1991) Retardation by aminoguanidine of development of albuminuria, mesangial cell expansion, and tissue fluorescence in streptozotocin-induced diabetic rat. Diabetes 40:1328–1334CrossRefPubMed

14.

Coppey LJ, Gellett JS, Davidson EP, Dunlop JA, Yorek MA (2002) Effect of treating streptozotocin-induced diabetic rats with sorbinil, myo-inositol or aminoguanidine on endoneurial blood flow, motor nerve conduction velocity and vascular function of epineurial arterioles of the sciatic nerve. Int J Diabetes Res 3:21–26CrossRef

15.

Aizu Y, Oyanagi K, Hu JG, Nakagawa H (2002) Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin-diabetic rats. Neuropathology 22:161–170CrossRefPubMed

16.

Dobler D, Ahmed N, Song LJ, Eboigbodin KE, Thornalley PJ (2006) Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification. Diabetes 55:1961–1969CrossRefPubMed

17.

Pedchenko VK, Chetyrkin SV, Chuang P et al (2005) Mechanism of perturbation of integrin–mediated cell-matrix interactions by reactive carbonyl compounds and its implication for pathogenesis of diabetic nephropathy. Diabetes 54:2952–2960CrossRefPubMed

18.

Rosca MG, Mustata TG, Kinter MT et al (2005) Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol 289:F420–F430CrossRefPubMed

19.

Yao D, Brownlee M (2009) Hyperglycemia-induced reactive oxygen species increase expression of RAGE and RAGE ligands. Diabetes 59:249–255CrossRefPubMed

20.

Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed

21.

Pomero F, Min AM, La Selva M, Allione A, Molinatti GM, Porta M (2001) Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose. Acta Diabetol 38:135–138CrossRefPubMed

22.

Alderson NL, Chachich ME, Frizzell N et al (2004) Effect of antioxidants and ACE inhibition on chemical modification of proteins and progression of nephropathy in the streptozotocin diabetic rat. Diabetologia 47:1385–1395CrossRefPubMed

23.

Kamata K, Ozawa Y, Kobayashi T, Matsumoto T (2009) Effect of N-epsilon-(carboxymethyl)lysine on coronary vasoconstriction in isolated perfused hearts from control and streptozotocin-induced diabetic rats. J Smooth Muscle Res 45:125–137CrossRefPubMed

24.

Forbes JM, Thomas MC, Thorpe SR, Alderson NL, Cooper ME (2004) The effects of valsartan on the accumulation of circulating and renal advanced glycation end products in experimental diabetes. Kidney Int 66:S105–S107CrossRef

25.

Williams SK, Howarth NL, Devenny JJ, Bitensky MW (2001) Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus. Proc Natl Acad Sci U S A 79:6546–6550CrossRef

26.

Cullum NA, Mahon J, Stringer K, Mclean WG (1991) Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus. Diabetologia 34:387–398CrossRefPubMed

27.

Delplanque J, Delpierre G, Opperdoes FR, van Schaftingen E (2004) Tissue distribution and evolution of fructosamine 3-kinase and fructosamine 3-kinase-related protein. J Biol Chem 279:46606–46613CrossRefPubMed

28.

Johnson RN, Easdale RW, Tatnell M, Baker JR (1991) Significance of variation in turnover of glycated albumin on indexes of diabetic control. Clin Chim Acta 198:229–238CrossRefPubMed

29.

Van Gompel J, Mahler T, Paepe M, Kloppel G (1993) Comparison of in situ hybridization and immunocytochemistry for the detection of residual beta cells in the pancreas of streptozotocin-treated diabetic rats. Acta Diabetol 30:118–122CrossRefPubMed

30.

Ahmed N, Thornalley PJ, Luthen R et al (2004) Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis. J Hepatol 41:913–919CrossRefPubMed

31.

Weissbach H, Resnick L, Brot N (2005) Methionine sulfoxide reductases: history and cellular role in protecting against oxidative damage. Biochim Biophys Acta 1703:203–212PubMed

32.

Ohshima H, Friesen M, Brouet I, Bartsch H (1990) Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins. Food Chem Toxicol 28:647–652CrossRefPubMed

33.

Naggar H, Ola MS, Moore P et al (2002) Downregulation of reduced-folate transporter by glucose in cultured RPE cells and in RPE of diabetic mice. Invest Ophthalmol Vis Sci 43:556–563

34.

Zill H, Bek S, Hofmann T et al (2003) RAGE-mediated MAPK activation by food-derived AGE and non-AGE products. Biochem Biophys Res Commun 300:311–313CrossRefPubMed

Titel: Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes
verfasst von: N. Karachalias
R. Babaei-Jadidi
N. Rabbani
P. J. Thornalley
Publikationsdatum: 01.07.2010
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 7/2010
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-010-1722-z

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Abstract

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