Understanding the mechanistic roles of microplastics combined with heavy metals in regulating ferroptosis: Adding new paradigms regarding the links with diseases

As a new type of pollutant, microplastics (MPs) commonly exist in today's ecosystems, causing damage to the ecological environment and the health of biological organisms, including human beings. MPs can function as carriers of heavy metals (HMs) to aggravate the enrichment of HMs in important organs of organisms, posing a great threat to health. Ferroptosis, a novel process for the regulation of nonapoptotic cell death, has been shown to be closely related to the occurrence and processes of MPs and HMs in diseases. In recent years, some HMs, such as cadmium (Cd), iron (Fe), arsenic (As) and copper (Cu), have been proven to induce ferroptosis. MPs can function as carriers of HMs to aggravate damage to the body. This damage involves oxidative stress, mitochondrial dysfunction, lipid peroxidation (LPO), inflammation, endoplasmic reticulum stress (ERS) and so on. Therefore, ferroptosis has great potential as a therapeutic target for diseases induced by MPs combined with HMs. This paper systematically reviews the potential effects and regulatory mechanisms of MPs and HMs in the process of ferroptosis, focusing on the mitochondrial damage, Fe accumulation, LPO, ERS and inflammation caused by MPs and HMs that affect the regulatory mechanism of ferroptosis, providing new insights for research on regulating drugs and for the development of ferroptosis-targeting therapy for Alzheimer's disease, Parkinson's disease, cancer and cardiovascular disease.