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J. Hazard. Mater., 2023 Aug 2;459:132208 | https://doi.org/10.1016/j.jhazmat.2023.132208 Unveiling potentially convergent key events related to adverse outcome pathways induced by silver nanoparticles via cross-species omics-scale analysis

Nguyen Hoang Anh ^a, Young Jin Min ^a, Truong Thi My Nhung ^b, Nguyen Phuoc Long ^c, Seunghyeon Han ^b, Sun Jo Kim ^a, Cheol Woon Jung ^a, Young Cheol Yoon ^a, Yun Pyo Kang^a, Sang Ki Park ^b, Sung Won Kwon ^a,d

^aCollege of Pharmacy, Seoul National University, Seoul 08826, the Republic of Korea
^bDepartment of Life Sciences, Pohang University of Science and Technology, Pohang 37673, the Republic of Korea
^cDepartment of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan 47392, the Republic of Korea
^dPlant Genomics and Breeding Institute, Seoul National University, Seoul 08826, the Republic of Korea

Correspondence to: Sung Won Kwon

Abstract

The adverse effects of silver nanoparticles (AgNPs) have been studied in various models. However, there has been discordance between molecular responses across the literature, attributed to methodological biases and the physicochemical variability of AgNPs. In this study, a gene pathway meta-analysis was conducted to identify convergent and divergent key events (KEs) associated with AgNPs and explore common patterns of these KEs across species. We performed a cross-species analysis of transcriptomic data from multiple studies involving various AgNPs exposure. Pathway enrichment analysis revealed a set of pathways linked to oxidative stress, apoptosis, and metabolite and lipid metabolism, which are considered potentially conserved KEs across species. Subsequently, experiments confirmed that oxidative stress responses could be early KEs in both Caenorhabditis elegans and HepG2 cells. Moreover, AgNPs preferentially impaired the mitochondria, as evidenced by mitochondrial fragmentation and dysfunction. Furthermore, disruption of amino acids, nucleotides, sulfur compounds, glycerolipids, and glycerophospholipids metabolism were in good agreement with gene pathway shreds of evidence. Our findings imply that, although there may be organism-specific responses, potentially conserved events could exist regardless of species and physicochemical factors. These results provide valuable insights into the development of adverse outcome pathways of AgNPs across species and the regulatory toxicity of AgNPs.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-08-21)
연구진국내 연구진
분야 의약학 > 약학

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