Chitosan Protects Peripheral Nerves Against Damage Induced by Diabetes Mellitus

Abstract

Background: Diabetic peripheral neuropathy (DPN) is one of the most common and debilitating complications of diabetes mellitus, for which current therapies do not prevent nerve degeneration. Chitosan, a biocompatible polysaccharide with antioxidant, anti-inflammatory, and lipid-lowering properties, may exert direct neuroprotective effects. This study evaluated the impact of oral administration of chitosan on peripheral nerve function and structure in a murine model of streptozotocin (STZ)-induced diabetes. Methods: Male C57BL/6 mice were divided into three groups: Sham, untreated diabetics (T1DM) and diabetics treated with chitosan (150 mg/kg/day, 12 weeks). Metabolic, behavioral (Open Field), nociceptive (Von Frey, Tail-Flick), electrophysiological (compound motor action potential—CMAP) and histological (intraepidermal nerve fiber density—IENF) parameters were analyzed. Results: Chitosan did not significantly modify blood glucose (p = 0.3366), but showed favorable metabolic effects, reducing LDL cholesterol in T1DM+Chitosan vs. T1DM mice (43.75 ± 5.62 mg/dL vs. 82.75 ± 7.65 mg/dL, p < 0.0001) as well as triglycerides (103.5 ± 12.8 mg/dL vs. 175.5 ± 22.8 mg/dL, p < 0.0001). In nociceptive tests, chitosan ameliorated thermal hyperalgesia (Tail-Flick: T1DM 1.25 ± 0.19 s vs. T1DM+Chitosan 1.54 ± 0.16 s; p = 0.0188) and mechanical allodynia (Von Frey: T1DM 0.16 ± 0.07 g vs. T1DM+Chitosan 0.38 ± 0.15 g, p = 0.0103). Electrodiagnostically, chitosan improved CMAP amplitude (T1DM 5.756 ± 0.706 mV vs. T1DM + Chitosan 6.756 ± 0.760 mV, p = 0.0409) and reduced CMAP duration (3.161 ± 0.217 ms vs. 2.900 ± 0.080 ms, p = 0.0273). Histologically, IENF density significantly increased in the treated group (0.01991 ± 0.00246 vs. 0.01512 ± 0.00253 in T1DM; p = 0.0200). Conclusions: Oral administration of chitosan confers functional and structural neuroprotection in STZ-induced diabetic neuropathy despite persistent hyperglycemia.