Aged nanoplastics exacerbate CPPD-induced ocular toxicity via the thyroxine pathway in zebrafish

Area of Science:

• Environmental Toxicology
• Nanotoxicology
• Ecotoxicology

Background:

• Naturally aged nanoplastics (NPs) and chemicals like N-cyclohexyl-N'-phenyl-p-phenylenediamine (CPPD) coexist in aquatic environments, posing complex risks.
• Understanding the combined toxicity of aged NPs and chemicals is crucial for ecological risk assessment.

Purpose of the Study:

• To evaluate the developmental and ocular toxicity of CPPD alone and co-exposed with aged polystyrene nanoplastics (PS-UV and PS-O₃) in embryonic zebrafish.
• To investigate the underlying mechanisms of combined toxicity and identify potential therapeutic interventions.

Main Methods:

• Embryonic zebrafish were exposed to CPPD, aged PS-UV, aged PS-O₃, and their combinations.
• Developmental endpoints (movement, response, heart rate, malformations) and ocular toxicity (abnormalities, behavior, cell death, inflammation) were assessed.
• Mechanistic studies involved evaluating thyroid hormone levels, oxidative stress markers, gene expression (Olig2, Huc, Mbp, cyp26a, opn1sw1), and the efficacy of n-phenylthiourea (PTU) and triiodothyronine (T3) treatments.

Main Results:

• Aged PS significantly exacerbated CPPD-induced developmental toxicity and ocular abnormalities, with PS-O₃ showing greater potency than PS-UV.
• Co-exposure led to increased ocular cell death, inflammation, and visual behavior deficits.
• PTU treatment effectively alleviated ocular toxicities, restored thyroid hormone balance, reduced apoptosis, and normalized gene expression related to the visual system, unlike T3.
• Biomarkers identified were highly correlated with ocular development indexes, indicating their potential as early toxicity indicators.

Conclusions:

• Aged nanoplastics synergistically amplify CPPD toxicity in zebrafish, impacting development and vision through disruption of oxidative stress, thyroid axis, and retinoid/phototransduction pathways.
• PTU shows potential as a therapeutic agent to mitigate nanoplastic-chemical co-exposure toxicity by restoring key physiological pathways.
• These findings provide critical insights for the ecological risk assessment of co-occurring nanoplastics and chemical pollutants.