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

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Title:	Use of an in silico knowledge discovery approach to determine mechanistic studies of silver nanoparticles-induced toxicity from in vitro to in vivo
Authors:	Mao, Bin-Hsu Luo, Yi-Kai Wang, Bour-Jr Jr Chen, Chun-Wan Cheng, Fong-Yu Lee, Yu-Hsuan Yan, Shian-Jang Wang, Ying-Jan
Contributors:	National Cheng Kung University Chia Nan University of Pharmacy & Science Chia Nan University of Pharmacy & Science National Cheng Kung University National Cheng Kung University Hospital Chinese Culture University China Medical University Taiwan National Cheng Kung University China Medical University Taiwan China Medical University Hospital - Taiwan
Keywords:	surface-coatings oxidative stress model organism mice lacking arrest cytotoxicity apoptosis cdk2 hyperplasia inhibition
Date:	2022
Issue Date:	2023-12-11 14:04:38 (UTC+8)
Publisher:	BMC
Abstract:	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.
Relation:	PARTICLE AND FIBRE TOXICOLOGY, v.19, n.CB2, pp.CC2, pp.-,
Appears in Collections:	[Offices] 123

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