Human Microplastics Exposure and Potential Health Risks to Target Organs by Different Routes: A Review

Ferroptosis is a recently recognized form of regulated cell death. It is characterized morphologically by the presence of smaller than normal mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, and outer mitochondrial membrane rupture. It can be induced by experimental compounds (e.g., erastin, Ras-selective lethal small molecule 3, and buthionine sulfoximine) or clinical drugs (e.g., sulfasalazine, sorafenib, and artesunate) in cancer cells and certain normal cells (e.g., kidney tubule cells, neurons, fibroblasts, and T cells). Activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of cystine/glutamate antiporter is involved in the induction of ferroptosis. This process is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism and can be pharmacologically inhibited by iron chelators (e.g., deferoxamine and desferrioxamine mesylate) and lipid peroxidation inhibitors (e.g., ferrostatin, liproxstatin, and zileuton). Glutathione peroxidase 4, heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators of ferroptosis by limiting ROS production and reducing cellular iron uptake, respectively. In contrast, NADPH oxidase and p53 (especially acetylation-defective mutant p53) act as positive regulators of ferroptosis by promotion of ROS production and inhibition of expression of SLC7A11 (a specific light-chain subunit of the cystine/glutamate antiporter), respectively. Misregulated ferroptosis has been implicated in multiple physiological and pathological processes, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, hepatic and heart ischemia/reperfusion injury, and T-cell immunity. In this review, we summarize the regulation mechanisms and signaling pathways of ferroptosis and discuss the role of ferroptosis in disease.

Plastic debris is an environmentally persistent and complex contaminant of increasing concern. Understanding the sources, abundance and composition of microplastics present in the environment is a huge challenge due to the fact that hundreds of millions of tonnes of plastic material is manufactured for societal use annually, some of which is released to the environment. The majority of microplastics research to date has focussed on the marine environment. Although freshwater and terrestrial environments are recognised as origins and transport pathways of plastics to the oceans, there is still a comparative lack of knowledge about these environmental compartments. It is highly likely that microplastics will accumulate within continental environments, especially in areas of high anthropogenic influence such as agricultural or urban areas. This review critically evaluates the current literature on the presence, behaviour and fate of microplastics in freshwater and terrestrial environments and, where appropriate, also draws on relevant studies from other fields including nanotechnology, agriculture and waste management. Furthermore, we evaluate the relevant biological and chemical information from the substantial body of marine microplastic literature, determining the applicability and comparability of this data to freshwater and terrestrial systems. With the evidence presented, the authors have set out the current state of the knowledge, and identified the key gaps. These include the volume and composition of microplastics entering the environment, behaviour and fate of microplastics under a variety of environmental conditions and how characteristics of microplastics influence their toxicity. Given the technical challenges surrounding microplastics research, it is especially important that future studies develop standardised techniques to allow for comparability of data. The identification of these research needs will help inform the design of future studies, to determine both the extent and potential ecological impacts of microplastic pollution in freshwater and terrestrial environments.