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Journal of Diabetes Research
Volume 2016, Article ID 8710432, 9 pages
http://dx.doi.org/10.1155/2016/8710432
Research Article

Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

1Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany
2Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
3Department of Cardiology, Pulmonology, Intensive Care and Vascular Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
4Department of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands

Received 8 May 2015; Revised 28 July 2015; Accepted 10 August 2015

Academic Editor: Sergiu Catrina

Copyright © 2016 Shiqi Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.