Polystyrene nanoplastics aggravates lipopolysaccharide‐induced apoptosis in mouse kidney cells by regulating IRE1/XBP1 endoplasmic reticulum stress pathway via oxidative stress

Abstract

Nanoplastics (NPs) pollution poses a huge threat to the ecosystem and has become one of the environmental pollutants that have attracted much attention. There is increasing evidence that both oxidative stress and endoplasmic reticulum stress (ERS) are associated with polystyrene nanoplastics (PS‐NPs) exposure. Lipopolysaccharide (LPS) has been shown to induce apoptotic damage in various tissues, but whether PS‐NPs can aggravate LPS‐induced apoptosis in mouse kidneys through oxidative stress‐regulated inositol‐requiring enzyme 1 (IRE1)/X‐box binding protein 1 (XBP1) ERS pathway remains unclear. In this study, based on the establishment of in vitro and in vivo PS‐NPs and LPS exposure models alone and in combination in mice and HEK293 cells, the effects and mechanisms of PS‐NPs on LPS‐induced renal cell apoptosis were investigated. The results showed that PS‐NPs could aggravate LPS‐induced apoptosis. PS‐NPs/LPS can induce ERS through oxidative stress, activate the IRE1/XBP1 pathway, and promote the expression of apoptosis markers (Caspase‐3 and Caspase‐12). Kidney oxidative stress, ERS, and apoptosis in PS‐NPs + LPS combined exposure group were more severe than those in the single exposure group. Interestingly, 4‐phenylbutyric acid‐treated HEK293 cells inhibited the expression of the IRE1/XBP1 ERS pathway and apoptotic factors in the PS‐NPs + LPS combined exposure group. N‐acetyl‐L‐cysteine effectively blocked the activation of the IRE1/XBP1 ERS pathway, suggesting that PS‐NPs‐induced oxidative stress is an early event that triggers ERS. Collectively, these results confirmed that PS‐NPs aggravated LPS‐induced apoptosis through the oxidative stress‐induced IRE1/XBP1 ERS pathway. Our study provides new insights into the health threats of PS‐NPs exposed to mammals and humans.

Mitochondria as a target of micro- and nanoplastic toxicity

“…In a study by Sun et al, exposure to PS NPs (size 20 nm) resulted in collapse of ΔΨm, an event associated with the activation of cellular apoptosis, at TM3 mouse Leydig cells (Sun et al, 2023b). This finding was reinforced by studies showing increased expression of apoptosis-related proteins in cells exposed to MPs/NPs, providing further evidence that these particles may interfere with the role of mitochondria in the regulation of apoptosis (Li et al, 2021;Wang et al, 2022b;Li et al, 2023b). In addition, the interaction of MPs/NPs with mitochondria could also affect cellular calcium homeostasis, as calcium is critical for several mitochondrial functions, including ATP production, this disruption could have significant consequences for cellular health.…”

Cellular and Systemic Effects of Micro- and Nanoplastics in Mammals—What We Know So Far

“…Investigating both HEK-293 cells and a murine in vivo model, Li et al showed that polystyrene NP can synergistically aggravate lipopolysaccharide (LPS)-induced renal cell apoptosis and the expression of the apoptosis markers Caspase-3 and Caspase-12 as well as endoplasmic reticulum stress through oxidative stress [50].…”

Microplastics and Kidneys: An Update on the Evidence for Deposition of Plastic Microparticles in Human Organs, Tissues and Fluids and Renal Toxicity Concern

“…Most of the studies performed on nanoplastics (NPs) and MPs’ toxicity on kidney have been published in the last two years. Li et al showed that PS-NPs worsen lipopolysaccharide-induced apoptosis in mouse kidney cells through the oxidative stress–endoplasmic reticulum pathway [ 38 ]. Furthermore, Tang et al demonstrate nephrotoxicity in mice related to inflammation, oxidative stress and lipid disturbance [ 39 ].…”