Work

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

Year: 2025

Type: article

Abstract: 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. With the continuous progress of industrialization and urbanization, plastic and chromium alloy products have been widely used in industrial and medical fields. Mounting evidence indicates that under the influence of various physical and chemical factors, these products release nanoparticles, leading to the formation of microplastics (MPs) and chromium nanoparticles (Cr NPs). These pollutants gradually accumulate in the human body and ultimately reach muscle tissues. Previous studies have demonstrated that MPs and Cr NPs can cause a certain degree of damage to muscle tissue; however, their combined toxic effects have not been reported. Our research reveals that MPs and Cr NPs can adsorb to each other, thereby increasing their chances of entering the body. Furthermore, both in vivo and in vitro experimental results indicate that co-exposure to MPs and Cr NPs results in more severe muscle inflammatory damage. Additionally, we found that co-exposure to MPs and Cr NPs activates the proteasome signaling pathway, and NAC (N-acetylcysteine) can inhibit the expression of the key gene PSMD2 in this pathway, subsequently suppressing inflammatory damage in muscle tissue. • The combined toxicity of MPs and Cr NPs on the muscular system is more pronounced, indicating severe health risks from their interaction. • MPs and Cr NPs accumulate in muscle tissue, leading to increased ROS levels, spinal deformities, and motor dysfunction. • MPs and Cr NPs activate the proteasome pathway by upregulating PSMD2 , mediating damage. • NAC alleviates oxidative stress and inflammation induced by MPs and Cr NPs, suggesting a therapeutic option for such pollution-related muscle damage.

Source: Environmental Pollution

DOI: 10.1016/j.envpol.2025.127387

Authors: Jie Dai, Yuxuan Du, Yunjia Wang, Guanteng Yang

Institutions: Central South University, Xinjiang Medical University, Sixth Affiliated Hospital of Xinjiang Medical University, Xiangya Hospital Central South University, Fourth Hospital of Changsha

Language: English

Topic: Microplastics and Plastic Pollution

Subfield: Pollution

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,090