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Войти в исследования Metabolism: clinical and experimental · 2015
The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN).
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Baum Petra, Kosacka Joanna, Estrela-Lopis Irina, Woidt Katrin, Serke Heike, Paeschke Sabine, Stockinger Maximilian, Klöting Nora, Blüher Matthias, Dorn Marco, Classen Joseph, Thiery Joachim, Bechmann Ingo, Toyka Klaus V, Nowicki Marcin
Аннотация
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.
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.