An in vitro – in vivo integrated approach for hazard and risk assessment of silver nanoparticles for soil organisms

Makama, Sunday

doi:10.18174/384962

Cited by 1 publication

(1 citation statement)

References 82 publications

(144 reference statements)

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“…In actual fact, differential surface charging attributed to the choice of coating agents has been shown to dictate the modalities of cell death evoked by various ENMs, inclusive of AgNPs [ 10 , 11 ]. Although the majority of documents have suggested that positively charged AgNPs are more toxic towards eukaryotic cells than negatively charged AgNPs, some conflicting in vivo evidence exists [ 12 , 13 ]. Accordingly, a more comprehensive study linking both in vitro cytotoxic profiling across multiple cell lines and in vivo systemic toxicity testing is desirable to elucidate how surface coatings contribute to toxicological impacts of AgNPs.…”

Section: Introductionmentioning

confidence: 99%

Use of an in silico knowledge discovery approach to determine mechanistic studies of silver nanoparticles-induced toxicity from in vitro to in vivo

et al. 2022

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Background Silver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic understanding of the size- and coating-dependent effects of AgNPs in vitro and in vivo remains elusive. We adopted an in silico decision tree-based knowledge-discovery-in-databases process to prioritize the factors affecting the toxic potential of AgNPs, which included exposure dose, cell type and AgNP type (i.e., size and surface coating), and exposure time. This approach also contributed to effective knowledge integration between cell-based phenomenological observations and in vitro/in vivo mechanistic explorations. Results The consolidated cell viability assessment results were used to create a tree model for generalizing cytotoxic behavior of the four AgNP types: SCS, LCS, SAS, and LAS. The model ranked the toxicity-related parameters in the following order of importance: exposure dose > cell type > particle size > exposure time ≥ surface coating. Mechanistically, larger AgNPs appeared to provoke greater levels of autophagy in vitro, which occurred during the earlier phase of both subcytotoxic and cytotoxic exposures. Furthermore, apoptosis rather than necrosis majorly accounted for compromised cell survival over the above dosage range. Intriguingly, exposure to non-cytotoxic doses of AgNPs induced G2/M cell cycle arrest and senescence instead. At the organismal level, SCS following a single intraperitoneal injection was found more toxic to BALB/c mice as compared to SAS. Both particles could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, along with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation. Conclusions Our integrated in vitro, in silico, and in vivo study revealed that AgNPs exerted toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure.

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