Chelation of dietary iron prevents iron accumulation and macrophage infiltration in the type I diabetic kidney.

Abstract

We previously reported that the functional deletion of p21, a cyclin-dependent kinase inhibitor, in mice attenuated renal cell senescence in streptozotocin (STZ)-induced type 1 diabetic mice. In the present study, we investigated the effect of iron chelation on renal cell senescence and inflammation in the type 1 diabetic kidney. STZ-treated mice showed increase in iron accumulation, tubular cell senescence and macrophage infiltration at week 28 in the kidney. Administering deferasirox, which removes only dietary iron, significantly attenuated iron accumulation in proximal tubules and the number of infiltrating F4/80-positive cells without effecting blood glucose, hematocrit or hemoglobin levels. In contrast however, deferasirox did not influence renal cell senescence. The lack of p21 decreased the renal tubular iron accumulation and did not change tubular cell senescence. Interestingly, the STZ-treated animals showed an increase in p16, another cyclin-dependent kinase inhibitor. The results suggest that type 1 diabetes increases renal tubular iron accumulation and macrophage infiltration through a p21-dependent mechanism, and that the chelation of dietary iron attenuates these responses.

• Authors: Tatsuyori Morita, Daisuke Nakano, Kento Kitada, Satoshi Morimoto, Atsuhiro Ichihara, Hirofumi Hitomi, Hiroyuki Kobori, Ichiro Shiojima, Akira Nishiyama
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 756 Pg. 85-91 (Jun 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25820160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Benzoates
• Cyclin-Dependent Kinase Inhibitor p21
• Iron Chelating Agents
• Iron, Dietary
• Triazoles
• Iron
• Deferasirox

Topics

• Animals
• Benzoates (pharmacology, therapeutic use)
• Cellular Senescence (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (deficiency, genetics)
• Deferasirox
• Diabetes Mellitus, Type 1 (complications)
• Diabetic Nephropathies (drug therapy, immunology, metabolism, pathology)
• Gene Knockout Techniques
• Iron (metabolism)
• Iron Chelating Agents (pharmacology, therapeutic use)
• Iron, Dietary
• Kidney (drug effects, immunology, metabolism, pathology)
• Macrophages (drug effects, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Triazoles (pharmacology, therapeutic use)