Biology 2022, 11, 1719. https://doi.org/10.3390/biology11121719 www.mdpi.com/journal/biology Article Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats Hanaa R. Aboelwafa, Ramadan A. Ramadan, Somaya S. Ibraheim and Hany N. Yousef * Biological and Geological Sciences Department, Faculty of Education, Ain Shams University, Cairo 11566, Egypt * Correspondence: hany_barsoum@edu.asu.edu.eg 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 nephrotoxi- city, 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 immunoreac- tivity was reduced. Most biochemical, histological, histomorphometrical, and immunohistochemi- cal 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, histo- pathological, 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 lev- els of the total antioxidant capacity, superoxide dismutase, catalase, reduced glutathione, and glu- tathione 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 Mal- pighian corpuscles and the proximal and distal convoluted tubules were decreased. Immunoreac- tivity for P53, caspase-3, and TNF-α reactive proteins were significantly increased; however, Bcl-2 immunoreactivity was decreased. Eug reversed most biochemical, histological, histomorphomet- rical, 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 nephrotoxi- city. Keywords: silver nanoparticles; eugenol; kidney; oxidative stress; histology; histopathology; immunohistochemistry Citation: Aboelwafa, H.R.; Ramadan, R.A.; Ibraheim, S.S.; Yousef, H.N. Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats. Biology 2022, 11, 1719. https://doi.org/10.3390/biology 11121719 Academic Editors: Haiyan Wang, Lei Xu and Zhen Yang Received: 5 November 2022 Accepted: 24 November 2022 Published: 27 November 2022 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institu- tional affiliations. Copyright: © 2022 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (https://cre- ativecommons.org/licenses/by/4.0/).