Chitosan Protects Peripheral Nerves Against Damage Induced by Diabetes Mellitus

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.

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.

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).

Oral administration of chitosan confers functional and structural neuroprotection in STZ-induced diabetic neuropathy despite persistent hyperglycemia.