Although, gold nanoparticles (GNPs) are attracting more and more attention due to their ease of synthesis, modification, and great potential value in biomedical applications, exhibited harmful effects on human health and other living species. Quercetin (Qur) clarifies diverse pharmacological effects, especially anti-inflammatory, antiapoptotic, and antioxidant ones. This study aimed to evaluate the probable nephrotoxicity induced by different diameters of sphere GNPs, as well as the nephroprotective role of Qur. A total of 54 healthy mature male albino rats were grouped and treated with or without sphere GNPs; 10, 20, and 50 nm and Qur (200 mg/kg b.wt.). The effects of GNPs and Qur were estimated through the collection of blood and kidney samples from euthanized rats and performed biochemical, histopathological, and immunohistochemical investigations. In comparison between different diameters of GNPs, the 10 nm GNPs revealed more significant elevations in all renal function parameters: creatinine, urea, blood urea nitrogen, and uric acid followed by 20 nm then 50 nm. Pre-cotreatment with Qur decreased all renal functional values. Histopathologically, 10 nm revealed the most potent renal pathological changes represented in the renal cortex with cloudy swelling of renal tubules, hypercellularity of some glomeruli, severe congestion of renal blood vessels, focal inter tubular edema, and vascular endotheliosis (degeneration of endothelium). In addition, the renal medulla revealed perivascular inflammatory cellular infiltration, perivascular fibrosis, intra tubular glycogen deposition, and casts deposition of mainly cellular casts. On the other hand, the Qur treatment ameliorated most of these pathological changes. The size of GNPs is pivotal in their pathological effect on renal tissues where the small-sized GNPs; 10 nm have more potent cytotoxic, inflammatory, and apoptotic effects rather than the larger ones. Otherwise, Qur clarified a significant mitigating role against the nephrotoxicity of the GNPs.
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