The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN)

Metabolism. 2016 Apr;65(4):391-405. doi: 10.1016/j.metabol.2015.11.002. Epub 2015 Nov 6.

Abstract

Background: Iron is an essential but potentially toxic metal in mammals. Here we investigated a pathogenic role of exogenous iron in peripheral diabetic neuropathy (PDN) in an animal model for type 1 diabetes.

Methods: Diabetes was induced by a single injection of streptozotocin (STZ) in 4-month-old Sprague-Dawley rats. STZ-diabetic rats and non-diabetic rats were fed with high, standard, or low iron diet. After three months of feeding, animals were tested.

Results: STZ-rats on standard iron diet showed overt diabetes, slowed motor nerve conduction, marked degeneration of distal intraepidermal nerve fibers, mild intraneural infiltration with macrophages and T-cells in the sciatic nerve, and increased iron levels in serum and dorsal root ganglion (DRG) neurons. While motor fibers were afflicted in all STZ-groups, only a low iron-diet led also to reduced sensory conduction velocities in the sciatic nerve. In addition, only STZ-rats on a low iron diet showed damaged mitochondria in numerous DRG neurons, a more profound intraepidermal nerve fiber degeneration indicating small fiber neuropathy, and even more inflammatory cells in sciatic nerves than seen in any other experimental group.

Conclusions: These results indicate that dietary iron-deficiency rather than iron overload, and mild inflammation may both promote neuropathy in STZ-induced experimental PDN.

Keywords: Iron; Nerve inflammation; Peripheral diabetic neuropathy; STZ-rats; Type 1 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetic Neuropathies / chemically induced*
  • Diabetic Neuropathies / pathology*
  • Diet
  • Ganglia, Spinal / pathology
  • Iron / blood
  • Iron, Dietary / toxicity*
  • Male
  • Nerve Fibers / pathology
  • Neural Conduction / drug effects
  • Neuritis / chemically induced*
  • Neuritis / pathology*
  • Neutrophil Infiltration / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / pathology
  • T-Lymphocytes / drug effects

Substances

  • Iron, Dietary
  • Iron