N-acetylcysteine suppresses proteasome pathway activation and muscular damage induced by microplastics and chromium nanoparticles

Under global plastic proliferation, microplastics (MPs) have become significant environmental pollutants. Annually, over one million patients undergo orthopedic surgeries involving chromium alloy implants, which release chromium nanoparticles (Cr NPs) during long-term intraosseous residence. These particles migrate to adjacent muscle tissues, potentially inducing adverse effects. This study aimed to investigate the combined impact of Cr NPs and MPs co-exposure on muscle systems and underlying mechanisms. Human tissue analysis confirmed concurrent Cr NPs and MPs accumulation in peri-implant regions. In vitro experiments showed elevated reactive oxygen species (ROS) levels and pro-inflammatory cytokine expression in C2C12 cells exposed to Cr NPs/MPs individually or combined, with synergistic enhancement under co-exposure conditions. Zebrafish models exhibited spinal deformities, reduced motility, and histopathological muscle damage following pollutant exposure. Mechanistic studies revealed proteasome pathway activation as a key mediator, evidenced by PSMD2 overexpression, Notably, N-acetylcysteine (NAC) pretreatment ameliorated co-exposure-induced muscle injury, reduced ROS accumulation, and inhibited proteasome activation. This research provides new perspectives on Cr NP/MP synergistic toxicity and identifies NAC as a potential therapeutic strategy against pollution-related muscle damage.