Long-term micro/nanoplastic ingestion promotes sepsis by worsening kidney damage: a transcriptomics and metabolomics study

Abstract

The harmful effects of micro/nanoplastics (MNPLs) to human health have garnered widespread attention, yet their impact on sepsis remains unclear. In this study, mice were fed with MNPLs of three different particle sizes for 10 weeks. A sepsis mouse model was then established using the caecal ligation and puncture (CLP) method, and the effects and potential mechanisms of long-term MNPL ingestion on septic mice were analysed using multi-omics techniques. The results showed that MNPL particles with a diameter of 0.1 microns exacerbated kidney damage in mice, leading to an increased mortality rate in septic mice. Multi-omics analysis revealed disruptions in amino acid metabolism pathways, particularly the arginine and proline metabolism pathways, in the kidneys of septic mice exposed to MNPLs. It was confirmed that Arg2 expression was significantly elevated in the septic animal models. A cell model was used to validate this finding, showing that Arg2 gene expression in HK2 cells exposed to MNPLs under septic conditions was also increased. After lentivirus-mediated knockdown of the Arg2 gene, the levels of SOD, GSH, and MDA in HK2 cells exposed to MNPLs during sepsis showed no significant differences compared to non-septic HK2 cells, suggesting an improved ability to resist oxidative stress. Based on these findings, we conclude that smaller-sized MNPLs pose a greater threat to septic mice by exacerbating kidney damage, thereby making difficult the prognosis of sepsis. This study demonstrated that the development of sepsis in mice with long-term MNPL intake was attributed to the abnormal expression of Arg-2 in renal tissue, potentially leading to exacerbating sepsis-induced kidney injury. However, further research is needed to confirm this hypothesis.