Apoptosis-mediated neurotoxicity and altered gene expression induced by silver nanoparticles

Abstract

Although not fully recognized, the neurotoxic effects of silver nanoparticles (Ag-NPs) are thought to occur through induction of oxidative stress and apoptosis. To investigate the exact underlying molecular mechanism, we aimed to explore the apoptotic effects of intraperitoneal injection of Ag-NPs and investigated the possible attributed changes in the mRNA expression of Bcl-2 and Bax genes in the rat hippocampus. Two in vivo sets of experiments, one to demonstrate apoptosis and the other to assess gene expression, were conducted on male Wistar rats. In each set, the first group, acting as control, received saline and the other three groups received Ag-NP at doses of 100, 200, and 400 ppm for five successive days. Ten days after the last injection, hippocampal tissue of the first set of rats was assessed for apoptosis using terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling staining. In the second set of experiments, mRNA expression of Bcl-2 and Bax genes was evaluated using real-time polymerase chain reaction. Ag-NP treatment was shown to induce apoptosis in a dose-dependent manner. Furthermore, Ag-NP reduced mRNA level of Bcl-2 in the rat hippocampal cells at all investigated doses compared to the control group ( p < 0.001). The mRNA level of Bax, on the other hand, was increased in these cells. The increase was significant compared to the control group at the doses of 200 ppm ( p < 0.05) and 400 ppm ( p < 0.001). Our results show that Ag-NPs reduce Bcl-2 and increase Bax genes expression, resulting in increased Bax/Bcl-2 ratios in rat hippocampal cells. This altered gene expression induces cell apoptosis and contributes to the neurotoxicity of Ag-NPs.

Toxic implications of silver nanoparticles on the central nervous system: A systematic literature review

“…AgNPs have found increased caspase levels and its expression (Chang et al, 2021;Gurunathan et al, 2019;Repar et al, 2018). In animal studies, observations such as hippocampal cell death increased caspase levels and its expression, increase in expression of Bax gene further corroborated the in vitro findings (Ghooshchian et al, 2017). Several researches conducted on various brain cells such as N2a, astrocyte, microglia, and primary rBMEC accounted for a dose-and time-dependent rise in inflammatory markers following AgNP exposure.…”

Mitigation of apoptosis-mediated neurotoxicity induced by silver nanoparticles via rutaceae nutraceuticals: P53 activation and Bax/Bcl-2 regulation

“…The results demonstrated that AgNPs induced dysfunction of brain tissue in addition to different oxidative stress that induced alternation on various biomarkers. Neurotoxic impact of AgNPs was illustrated in several studies utilizing different particle sizes [13] , [17] . Exposure to AgNPs, can cause toxicity in different organs, inclusive the brain and nervous system [39] , [40] , [41] .…”

“…Bcl-2 is a protein family which determines cells involvement in apoptosis through mitochondrial interaction. Bcl-2 and other anti-apoptotic biomarkers could inhibit apoptosis, meanwhile Bax as a pro-apoptotic biomarker has the ability to induce apoptosis [15] , [16] , [17] .…”

Species-specific sensitivity of Eisenia earthworms towards noble metal nanoparticles: a multiparametric in vitro study

“…By means of TUNEL assay a previous study 49 has reported that AgNP treatments caused DNA damages in THP-1 monocytic cell line which could be linked to excess ROS production. Furthermore, in rat hippocampus AgNPs induced apoptosis in a dose-dependent manner observed by TUNEL staining 50 . Likewise Ribeiro et al, (2019) 51 documented apoptosis of E. fetida coelomocytes upon copper oxide nanomaterial exposure in vitro.…”