Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats

SIMPLE SUMMARY: The main objective of this study is to assess how eugenol (Eug) affects AgNP-induced nephrotoxicity in rats. After 30 days of treatment with AgNPs, rats developed nephrotoxicity, which was characterized by disruptions in the serum levels of blood urea nitrogen, creatinine, uric acid, the total oxidant capacity, the total antioxidant capacity, and interfering levels of kidney injury molecule-1, superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, malondialdehyde, tumor necrosis factor-alpha (TNF-α), and interleukin-6 in kidney tissues. These biochemical alterations were accompanied by the destruction of normal renal architecture, with most renal components shedding their thickness, diameter, and quantity. Furthermore, P53, Caspase3, and TNF-α immunoreactivity were considerably elevated; however, Bcl-2 immunoreactivity was reduced. Most biochemical, histological, histomorphometrical, and immunohistochemical alterations in AgNP-treated rats were reversed by Eug. We may infer that Eug has a protective effect against AgNP-induced nephrotoxicity. ABSTRACT: The use of silver nanoparticles (AgNPs) is expanding. This study evaluates the modulator effect of eugenol (Eug) on AgNP-induced nephrotoxicity in rats. Sixty male rats were separated into six groups: control, Eug, AgNPs low-dose, AgNPs high-dose, Eug + AgNPs low-dose, and Eug + AgNPs high-dose. After 30 days, kidney function, antioxidative and proinflammatory status, histopathological, histomorphometrical, and immunohistochemical assessments were performed. AgNPs markedly induced oxidative stress in renal tissues, characterized by increased levels of blood urea nitrogen, creatinine, uric acid, kidney injury molecule-1, the total oxidant capacity, malondialdehyde, tumor necrosis factor-alpha (TNF-α), and interleukin-6, as well as decreased levels of the total antioxidant capacity, superoxide dismutase, catalase, reduced glutathione, and glutathione peroxidase. Moreover, the normal renal architecture was destroyed, and the thickness of the renal capsules, cortex, and medulla, alongside the diameter and quantity of the normal Malpighian corpuscles and the proximal and distal convoluted tubules were decreased. Immunoreactivity for P53, caspase-3, and TNF-α reactive proteins were significantly increased; however, Bcl-2 immunoreactivity was decreased. Eug reversed most biochemical, histological, histomorphometrical, and immunohistochemical changes in AgNP-treated animals. This study demonstrated that nephrotoxicity in AgNP-treated rats was mitigated by an Eug supplementation. Eug’s antioxidant, antiapoptotic, and anti-inflammatory capabilities were the key in modulating AgNPs nephrotoxicity.