Resveratrol in Microplastic- and Nanoplastic-Induced Toxicity: Current Evidence, Mechanistic Insights, and Future Directions.

Microplastic (MP; MPs) and nanoplastic (NP; NPs) pollution poses a growing threat to global health. Their small size and large surface area facilitate ingestion, accumulation, and interactions with biological systems, leading to toxicity through oxidative stress, inflammation, mitochondrial dysfunction, and cell death. These effects may occur directly or through the release of adsorbed pollutants and plastic additives. Resveratrol (3,5,4'-trihydroxy-trans-stilbene; RV), a natural polyphenol found in grapes, berries, and peanuts, has attracted interest as a potential protective agent because of its antioxidant and anti-inflammatory properties. Its proposed protective effects against MP/NP toxicity involve modulation of key cellular signaling pathways, particularly nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB). RV may activate Nrf2 by disrupting its interaction with Kelch-like ECH-associated protein 1 (Keap1), thereby enhancing antioxidant defenses, including superoxide dismutase, catalase, and glutathione peroxidase, and reducing reactive oxygen species-mediated damage to lipids, proteins, and DNA. Concurrently, RV may suppress NF-κB-mediated inflammatory responses. However, current evidence is limited to a small number of preclinical studies, with no human studies available. These mechanisms remain largely hypothetical and require validation using standardized MP/NP exposure models.