The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms

Abstract

Background Silver nanoparticles (AgNPs) can accumulate in various organs after oral exposure. The main objective of the current study is to evaluate the renal toxicity induced by AgNPs after repeated oral exposure and to determine the relevant molecular mechanisms. Methods In this study, 40 male Wistar rats were treated with solutions containing 30, 125, 300, and 700 mg/kg of AgNPs. After 28 days of exposure, histopathological changes were assessed using hematoxylin-eosin (H&E), Masson’s trichrome, and periodic acid-Schiff (PAS) staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and the level of expression of the mRNAs of growth factors was determined using RT-PCR. Results Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border, and interrupted tubular basal laminae. These changes were more noticeable in groups treated with 30 and 125 mg/kg. The collagen intensity increased in the group treated with 30 mg/kg in both the cortex and the medulla. Apoptosis was much more evident in middle-dose groups (i.e., 125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in the treated groups (p < 0.05). Moreover, the data related to EGF, TNF-α, and TGF-β1 revealed that AgNPs induced significant changes in gene expression in the groups treated with 30 and 700 mg/kg compared to the control group. Conclusion Our observations showed that AgNPs played a critical role in in vivo renal toxicity.

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

“…ROS may interact with macromolecules inside the cells, severely harming biological components [ 51 ]. In line with our findings, other investigations have demonstrated that AgNPs generate oxidative stress in kidney tissues [ 41 , 44 ].…”

“…The animals treated with AgNPs suffered from nephrotoxicity and experienced a severe renal failure [ 43 ]. These results may be explained by the possibility that AgNP-induced oxidative stress promotes the generation of many vasoactive mediators, which can impair the renal function by causing renal vasoconstriction or by lowering the glomerular capillary ultra-filtration coefficient, which consequently decreases the glomerular filtration rate [ 44 ]. Note that an oral administration of Eug to AgNP-treated rats restored the serum levels of BUN, creatinine, and uric acid, suggesting that Eug offers a defense against AgNP-induced nephrotoxicity.…”

Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors

“…On the other hand, intra-arterial injection of nanoparticles carries risks of increased nanoparticle binding to blood components and can potentially lead to thrombi or stenosis. Moreover, during the therapy, circulating nanoparticles may interact with the kidneys [49,50], leading to a worst-case renal tubule blockage. Accordingly, a prerequisite for the preparation of nanoparticles will be the maximum delineation of nanoparticle sizes that are safe for administration to animals and, subsequently, to humans.…”

Plant Extract-Synthesized Silver Nanoparticles for Application in Dental Therapy

“…These phenomena were demonstrated in various human cell lines (keratinocytes, [147], hepatic, neuronal, lung epithelial, and murine stem cells), as well as animal tissues and organs [147]. Repeated exposure to AgNPs can potentiate inflammatory responses, activate the innate immunity [148], and have been associated with renal- [149], hepatic-and genotoxicity [147]. Even at non-cytotoxic doses, repeated doses of AgNPs may be detrimental to vital organs, resulting in their dysfunction and possibly total organ failure [150].…”