Exploring toxicological pathways of microplastics and nanoplastics: Insights from animal and cellular models.

Microplastics (MPs) and nanoplastics (NPs) represent an emerging issue for human and animal health. This review critically examines in vitro and in vivo studies to elucidate their mechanisms of action and toxicological effects. Key objectives included: providing a comprehensive overview of MP-NPs studies in literature, assessing experimental conditions relative to real environmental scenarios, and identifying toxicological pathways at the molecular level. The findings revealed significant progress in understanding MP-NPs impacts. In particular, it has been observed the promotion of inflammation, oxidative stress, apoptosis, autophagy, and endoplasmic reticulum (ER) stress via specific signaling axes. Reproductive toxicity emerged as the primary research focus, particularly in male models, whereas effects on gastrointestinal, neurological, and cardiovascular systems were insufficiently studied, especially for the molecular pathways affected. Most studies disproportionately focused on polystyrene particles, neglecting other prevalent polymers such as polyethylene and polypropylene. Furthermore, reliance on synthetic microspheres and non-realistic experimental concentrations limits relevance to real-world conditions. Limited long-term exposure studies further constrain the understanding of MP-NPs persistence and risks. In view of this, future research should integrate environmentally relevant conditions for particles doses, size and composition, long-term exposure assessments, and advanced methodologies such as omics and computational modeling. In addition, therapeutic interventions targeting oxidative and ER stress, inflammation and apoptosis may be an excellent solution to mitigate MP-NPs toxicity. At the same time, a standardized global approach is needed to fully understand the risks posed by MP-NPs, attempting to safeguard public and environmental health.