Neuropathy Induced by Exogenously Administered Advanced Glycation End-products in Rats

Overview

Journal J Diabetes Investig

Specialty Endocrinology

Date 2014 May 21

PMID 24843407

Citations 10

Authors

Yusuke Nishizawa

Ryu-Ichi Wada

Masayuki Baba

Masayoshi Takeuchi

Chieko Hanyu-Itabashi

Soroku Yagihashi

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Aims/Introduction: Advanced glycation end-products (AGE) have been implicated in the development of diabetic neuropathy. It still remains unknown, however, how AGE cause functional and structural changes of the peripheral nerve in diabetes. To explore the role of AGE in diabetic neuropathy, we examined the peripheral nerve by injecting AGE into normal Wistar rats.

Materials And Methods: Young, normal male Wistar rats were injected intraperitoneally (i.p.) daily for 12 weeks with purified AGE prepared by incubating D-glucose with bovine serum albumin (BSA). A control group received BSA alone. A group of rats given AGE were co-treated with aminoguanidine (50 mg/kg/day, i.p.). Peripheral nerve function and structure, as well as nerve Na(+),K(+)-ATPase activity, were examined in these rats. Immunohistochemical expressions of 8-hydroxy-2'-deoxyguanosine (8OHdG) and nuclear factor-κB (NF-κB)p65 were also examined.

Results: Serum AGE levels were increased two to threefold in the AGE-treated group compared with those in the BSA-treated control group. AGE-treated rats showed a marked slowing of motor nerve conduction velocity (MNCV) and decreased nerve Na(+),K(+)-ATPase activity compared with those in the BSA-treated group. These changes were accompanied by intensified expressions of 8OHdG and NF-κBp65 in endothelial cells and Schwann cells. Aminoguanidine treatment corrected MNCV delay, Na(+),K(+)-ATPase activity, and suppressed the expression of 8OHdG and NF-κB, despite there being no influence on serum AGE levels.

Conclusions: The results suggest that an elevated concentration of blood AGE might be one of the contributing factors to the development of neuropathic changes in diabetes.

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References

Cameron N, EATON S, Cotter M, Tesfaye S . Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia. 2001; 44(11):1973-88. DOI: 10.1007/s001250100001. View

Vlassara H, Striker L, Teichberg S, Fuh H, Li Y, Steffes M . Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. Proc Natl Acad Sci U S A. 1994; 91(24):11704-8. PMC: 45300. DOI: 10.1073/pnas.91.24.11704. View

Haslbeck K, Schleicher E, Bierhaus A, Nawroth P, Haslbeck M, Neundorfer B . The AGE/RAGE/NF-(kappa)B pathway may contribute to the pathogenesis of polyneuropathy in impaired glucose tolerance (IGT). Exp Clin Endocrinol Diabetes. 2005; 113(5):288-91. DOI: 10.1055/s-2005-865600. View

Takeuchi M, Bucala R, Suzuki T, Ohkubo T, Yamazaki M, Koike T . Neurotoxicity of advanced glycation end-products for cultured cortical neurons. J Neuropathol Exp Neurol. 2001; 59(12):1094-105. DOI: 10.1093/jnen/59.12.1094. View

Toth C, Rong L, Yang C, Martinez J, Song F, Ramji N . Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy. Diabetes. 2007; 57(4):1002-17. DOI: 10.2337/db07-0339. View

Sima A, Sugimoto K . Experimental diabetic neuropathy: an update. Diabetologia. 1999; 42(7):773-88. DOI: 10.1007/s001250051227. View

Wada R, Nishizawa Y, Yagihashi N, Takeuchi M, Ishikawa Y, Yasumura K . Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy. Eur J Clin Invest. 2001; 31(6):513-20. DOI: 10.1046/j.1365-2362.2001.00826.x. View

Malberti F, Surian M, Farina M, Vitelli E, Mandolfo S, Guri L . Effect of hemodialysis and hemodiafiltration on uremic neuropathy. Blood Purif. 1991; 9(5-6):285-95. DOI: 10.1159/000170026. View

Sugimoto K, Nishizawa Y, Horiuchi S, Yagihashi S . Localization in human diabetic peripheral nerve of N(epsilon)-carboxymethyllysine-protein adducts, an advanced glycation endproduct. Diabetologia. 1998; 40(12):1380-7. DOI: 10.1007/s001250050839. View

10.

Schmidt A, Hasu M, Popov D, Zhang J, Chen J, Yan S . Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. Proc Natl Acad Sci U S A. 1994; 91(19):8807-11. PMC: 44695. DOI: 10.1073/pnas.91.19.8807. View

11.

Yagihashi S, Kamijo M, Baba M, Yagihashi N, Nagai K . Effect of aminoguanidine on functional and structural abnormalities in peripheral nerve of STZ-induced diabetic rats. Diabetes. 1992; 41(1):47-52. DOI: 10.2337/diab.41.1.47. View

12.

Obrosova I, Van Huysen C, Fathallah L, Cao X, Stevens M, Greene D . Evaluation of alpha(1)-adrenoceptor antagonist on diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense. FASEB J. 2000; 14(11):1548-58. DOI: 10.1096/fj.14.11.1548. View

13.

Schmidt A, Hori O, Chen J, Li J, Crandall J, Zhang J . Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of.... J Clin Invest. 1995; 96(3):1395-403. PMC: 185762. DOI: 10.1172/JCI118175. View

14.

Monnier V, Kohn R, Cerami A . Accelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci U S A. 1984; 81(2):583-7. PMC: 344723. DOI: 10.1073/pnas.81.2.583. View

15.

Yan S, Schmidt A, Anderson G, Zhang J, Brett J, Zou Y . Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem. 1994; 269(13):9889-97. View

16.

Vlassara H, Fuh H, Donnelly T, Cybulsky M . Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits. Mol Med. 1995; 1(4):447-56. PMC: 2229997. View

17.

Vlassara H, Fuh H, Makita Z, Krungkrai S, Cerami A, Bucala R . Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad Sci U S A. 1992; 89(24):12043-7. PMC: 50694. DOI: 10.1073/pnas.89.24.12043. View

18.

Sugimoto K, Yagihashi S . Effects of aminoguanidine on structural alterations of microvessels in peripheral nerve of streptozotocin diabetic rats. Microvasc Res. 1997; 53(2):105-12. DOI: 10.1006/mvre.1996.2002. View

19.

Takeuchi M, Makita Z, Yanagisawa K, Kameda Y, Koike T . Detection of noncarboxymethyllysine and carboxymethyllysine advanced glycation end products (AGE) in serum of diabetic patients. Mol Med. 1999; 5(6):393-405. PMC: 2230431. View

20.

Ikeda K, Nagai R, Sakamoto T, Sano H, Araki T, Sakata N . Immunochemical approaches to AGE-structures: characterization of anti-AGE antibodies. J Immunol Methods. 1998; 215(1-2):95-104. DOI: 10.1016/s0022-1759(98)00064-7. View