Evaluating Hepatic Toxicity of Chitosan and Chitosan- Functionalized Iron Oxide Nanoparticles in a Rat Model of Peripheral Nerve Injury — Relevance for Rehabilitation Medicine

Abstract

Background: Peripheral nerve injuries (PNI) can generate important medium- and long-term disability, as patients mostly complain about associated pain, sensibility and, or motor deficit, and even psychological manifestations. Chitosan and different nanoparticles types were previously used in several studies as treatment of peripheral nerve injuries. The present study aimed to assess the hepatic responses at oral administration of simple chitosan solution and of magnetic iron oxide nanoparticles functionalized with chitosan (CMNPs) solution in an experimentally induced peripheral nerve injury. (2) Methods: Chitosan or CMNPs were oral administrated, for 21 days, to animals with peripheral nerve injury. The treated groups were compared with a control group (peripheric nerve injury without any treatment). The hepatic toxicity of administered solutions was analyzed histologically, through transmission electron microscopy (TEM) and through the oxidative stress parameters, in comparison with the control group. (3) Results: Liver tissue histological evaluation showed non-significant degeneration of hepatocytes in Chitosan group and, in CMNPs group, slight periportal inflammation. TEM investigation revealed nuclear and mitochondrial polymorphism and lipid accumulation in hepatocytes in Chitosan group, and in CMNPs group, irregular nucleus profiles and increased glycogen storage in cytosol. Oxidative stress analysis showed antioxidant hepatic effect of both treatments. (4) Conclusions: Compared to control group, both treatments produced significant increases of hepatic antioxidant protection, probably induced by chitosan properties. Histological modifications of the liver were minimal for both treatment groups. TEM investigation showed unspecific alterations of the hepatocytes structure. Keywords: chitosan; iron oxide magnetic nanoparticles; peripheral nerve injury; toxicity