Abstract
The purpose of this article was to explore the effects of gold nanoparticles (GNPs) and silver nanoparticles (SNPs) with different cytotoxicities on human dermal fibroblasts (HDFs) at the metabolic level. First, ∼20 nm of GNPs and SNPs were prepared, and their effects on the proliferation of HDFs were evaluated. Then, a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4, 8 and 24 h of treatment. Furthermore, the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments. The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h, while the cytotoxicity of the SNPs reached grade 1 after 72 h. By using metabolomics analysis, 29, 30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment, while SNPs induced the differential expression of 13, 33 and 22 metabolites after 4, 8 and 24 h of treatment, respectively. Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis, respectively. The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway (the key metabolite of which was glutathione) and the citrate cycle pathway (the key metabolite of which was malic acid). Based on the experiments used to verify the key metabolites and key metabolic pathways, it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity. After exposure to SNPs, the citric acid content was increased, mainly through the citrate cycle pathway, thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.