Ameliorative effect of chitosan nanoparticles against carbon tetrachloride-induced nephrotoxicity in Wistar rats

Context: Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications. Objective: This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats. Materials and methods: Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl₄-induced nephrotoxicity (untreated), and two groups receiving CCl₄ + chitosan NPs (10 and 20 mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-κB and COX-2 in renal tissues. Results: Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20 mg/kg) concurrently with CCl₄ for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20 mg/kg) revealed a significant (p ˂ 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-α (33.6%), interleukin-1β (31.1%), and caspase-3 (36.6%). Conclusions: Chitosan nanoparticles afforded significant protection and amelioration against CCl₄-induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications.