With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed in vitro. Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics.

This study represents the green synthesis of silver nanoparticles (AgNPs) using Ipomoea aquatica (Water Spinach) leaf extract, and investigate the cytotoxicity and antimicrobial activities. The Ipomoea aquatica (IA) mediated green synthesized AgNPs (IA-AgNPs) was characterized by ultraviolet–visible (UV–VIS.) spectrophotometry, Fourier transform-infrared (FT-IR) spectroscopy, atomic absorption spectrometry (AAS), X-ray deffractometry (XRD), transmission electron microscopy (TEM), and energy dispersive X-ray (EDX) spectroscopy. The results showed that the material was formed in nano-dimension with particle size in the range between 15–30 nm. The nanoparticles (NPs) were almost spherical in shape and demonstrated excellent material stability. The PC12 cell model in-vitro was used to determine the cytotoxicity of the IA-AgNPs, and for antimicrobial study, E. coli, Salmonella, and Staphylococcus sp. were employed. The cell viability results showed that the NPs did not induce any cytotoxicity until 10 ppm for 48 h of incubation, and it was further confirmed by the lactate dehydrogenase (LDH) assay. Moreover, IA-AgNPs demonstrated good antibacterial activity against three bacteria: E. coli, Salmonella, and Staphylococcus sp. Thus, this study may create an important synthetic route for the production of green-AgNPs and their safe usages, and may also be used to augment the bioactivities of the material with minimum toxicity. GRAPHICAL ABSTRACT

Several subunits in the matrix domain of mitochondrial complex I (CI) have been posited to be redox sensors for CI, but how elevated levels of reactive oxygen species (ROS) impinge on CI assembly is unknown. We report that genetic disruption of the mitochondrial NADPH-generating enzyme, isocitrate dehydrogenase 2 (IDH2), in Drosophila flight muscles results in elevated ROS levels and impairment of assembly of the oxidative phosphorylation system (OXPHOS). Mechanistically, this begins with an inhibition of biosynthesis of the matrix domain of CI and progresses to involve multiple OXPHOS complexes. Despite activation of multiple compensatory mechanisms, including enhanced coenzyme Q biosynthesis and the mitochondrial unfolded protein response, ferroptotic cell death ensues. Disruption of enzymes that eliminate hydrogen peroxide, but not those that eliminate the superoxide radical, recapitulates the phenotype, thereby implicating hydrogen peroxide as the signaling molecule involved. Thus, IDH2 modulates the assembly of the matrix domain of CI and ultimately that of the entire OXPHOS.

Mercury (Hg) in its all forms, including inorganic Hg (iHg) is an environmental contaminant due to toxicity and diseases in human. However, a little is known about the underlying mechanisms responsible for iHg toxicity. Selenium (Se) is an essential trace element, recognized as an antioxidant and protective agent against metal toxicities. The purpose of this research was to investigate ameliorations of Se counter to iHg-mediated toxicity in PC12 cells. Cytotoxic assays have been shown that iHg (5 μM) caused oxidative stress and intrinsic apoptosis via ROS generation, oxidizing glutathione, damaging DNA, degrading cell membrane integrity, down-regulating mTOR, p-mTOR, akt and ERK1, and up-regulating cleaved caspase 3 and cytochrome c release in PC12 cells 48 h after incubation. Co-treatment of Se (5 μM) inhibited intrinsic apoptosis and oxidative stress induced by iHg (5 μM) via inhibiting ROS formation, boosting GPx contents, increasing reduced glutathione, limiting DNA degradation, improving cell membrane integrity, up-regulating mTOR, p-mTOR, akt, ERK1 and caspase 3, and down-regulating cleaved caspase 3 and cytochrome c leakage in PC12 cells. In conclusion, these results recommended that excessive ROS generation acts a critical role in iHg-influenced oxidative stress and co-treatment of Se attenuates iHg-cytotoxicity through its antioxidant properties.