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

Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications.

This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats.

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.

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%).

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.