4.7 Article

Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells

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BIOMEDICINE & PHARMACOTHERAPY
卷 160, 期 -, 页码 -

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2023.114316

关键词

Sulforaphane; Adverse outcome pathway; Toxicology systems approach; Skin diseases; Chromosomal damage

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This study aimed to generate SFN-triggered adverse outcome pathway (AOP) by examining the relationship between SFN chemical structure and its toxicity, as well as SFN-gene interactions. The study found that SFN may cause chromosomal damage, skin sensitization, and bacterial mutagenicity. Gene interaction analysis revealed connections between SFN and chromosomal damage and skin diseases. Network analysis showed the involvement of these genes in broader networks. Overall, SFN is implicated in adverse outcomes, particularly chromosomal damage and skin diseases.
Sulforaphane (SFN) is a naturally occurring molecule present in plants from Brassica family. It becomes bioactive after hydrolytic reaction mediated by myrosinase or human gastrointestinal microbiota. Sulforaphane gained scientific popularity due to its antioxidant and anti-cancer properties. However, its toxicity profile and potential to cause adverse effects remain largely unidentified. Thus, this study aimed to generate SFN-triggered adverse outcome pathway (AOP) by looking at the relationship between SFN-chemical structure and its toxicity, as well as SFN-gene interactions. Quantitative structure-activity relationship (QSAR) analysis identified 2 toxophores (Derek Nexus software) that have the potential to cause chromosomal damage and skin sensitization in mammals or mutagenicity in bacteria. Data extracted from Comparative Toxicogenomics Database (CTD) linked SFN with previously proposed outcomes via gene interactions. The total of 11 and 146 genes connected SFN with chro-mosomal damage and skin diseases, respectively. However, network analysis (NetworkAnalyst tool) revealed that these genes function in wider networks containing 490 and 1986 nodes, respectively. The over -representation analysis (ExpressAnalyst tool) pointed out crucial biological pathways regulated by SFN-interfering genes. These pathways are uploaded to AOP-helpFinder tool which found the 2321 connections between 19 enriched pathways and SFN which were further considered as key events. Two major, interconnected AOPs were generated: first starting from disruption of biological pathways involved in cell cycle and cell pro-liferation leading to increased apoptosis, and the second one connecting activated immune system signaling pathways to inflammation and apoptosis. In both cases, chromosomal damage and/or skin diseases such as dermatitis or psoriasis appear as adverse outcomes.

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