Mitigating cardiotoxicity and nephrotoxicity: the role of naringin-dextrin nanoparticles in male Wistar rats

Nanoparticles are the fundamental building blocks of nanotechnology with numerous scientific applications. New advancements in nanotechnology have revealed uses for nanoparticles in various medicinal applications. This study investigated the chemoprotective effects of naringin-dextrin nanoparticles (NNPs) against diethylnitrosamine (DEN)-induced cardio-nephrotoxicity in Wistar rats. Cardio-nephrotoxicity was induced in Wistar rats via intraperitoneal DEN injection (150 mg/kg body weight (b.w.) per week) for 2 weeks, followed by oral administration of 2-acetylaminofluorene (2AAF) (20 mg/kg b.w.) four times per week for 3 weeks. Rats were then treated every other day for 24 weeks with either 10 mg/kg body weight of naringin (Nar) or 10 mg/kg body weight of NNPs. Nar and NNP treatments reduced biochemical markers of heart and kidney and improved tissue morphology compared to the DEN-treated group. These results were linked to a notable reduction in malondialdehyde (MDA) and nitric oxide (NO) levels, upregulation of antioxidant enzyme superoxide dismutase (SOD) activity, and enhanced glutathione (GSH) and nuclear factor erythroid 2-related factor 2 protein (NRF2) expression in the heart and kidneys. Nar and NNPs exerted an anti-inflammatory effect, manifested by a decrease in heart and kidney protein expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), with a concurrent increase in interleukin-4 (IL-4) expression, though this effect was more potent with NNPs than Nar. Regarding the effect on apoptosis, both Nar and NNPs significantly reduced the protein expression of p53 and caspase-3. Nar and NNPs effectively improved oxidative stress, inflammation, and tissue damage associated with DEN/AAF-induced cardio-nephrotoxicity.