Examining the impact of nanoplastics and PFAS exposure on immune functions through inhibition of secretory immunoglobin A in human breast milk.

Emerging contaminants such as nanoplastics (NPs) and per- and polyfluoroalkyl substances (PFAS), have been detected in the environment and breast milk, thus exposing infants to potentially harmful chemicals during breastfeeding. Breast milk contains secretory immunoglobulin A (SIgA), an antibody that plays a vital role in disease protection and the development of the infant's immune system. This study employed molecular simulation and fractional factorial designs to assess the toxicity of NPs and PFAS on breast milk and their influence on infant immunity by inhibiting SIgA. The research found that NPs and PFAS have higher binding affinities to SIgA compared to the control compound. Polycarbonate (-10.7 kcal/mol) had the highest binding affinity among plastics, while Perfluorodecanoic acid (PFDA, - 8.0 kcal/mol) had the highest binding affinity among PFAS. The relative toxic index was higher for PFAS (2.4) than for plastics (1.9), suggesting that PFAS may pose a higher overall toxicity burden on the protein. The presence of specific combinations of NPs and PFAS in breast milk may potentially harm breastfeeding infants, although additional experimental studies are required to validate these findings. These results underscore the potential risks associated with these emerging contaminants in breast milk and their impact on infant immunity.

Evaluation of nanoplastics toxicity to the human placenta in systems.

Following the discovery of plastics in the human placenta, this study evaluated the toxicity of ten different nanoplastics (NPs) in the human placenta. Since the placenta performs metabolic and excretion functions by the enzymatic system, the NPs were docked on these human enzymes including soluble epoxide hydrolase, uracil phosphoribosyltransferase, beta 1,3-glucuronyltransferase I, sulfotransferase, N-acetyltransferase 2, and cytochrome P450 1A1at their active sites with toxicity (binding affinity) determined and compared to control compounds. Density functional theory analysis were conducted on the NPs to identify their global reactivity descriptors and Artificial Neural Networks to predict toxicity based on reactivity descriptors. Polycarbonate (PC), polyethylene terephthalate (PET) and polystyrene (PS) showed the highest toxicity to all enzymes and thus the most toxic polymers due to the presence of an electron-withdrawing group in their aromatic rings, which demonstrated an improved recognition of the enzyme active site by pi- and alkyl interactions. A 210-6 fractional factorial design approach was used in conjunction with a fixed effects model to assess the primary and secondary effects of NPs in a composite system on binding affinity to the placental enzymes. The simulation results suggest that NPs mixture may pose significant risks to the placenta through inhibition of its key enzymes.

Toxicity evaluation of microplastics to aquatic organisms through molecular simulations and fractional factorial designs.

Molecular docking, molecular dynamics modelling, and fractional factorial design methodologies were used in the current work to examine the harmful effects of ten microplastic (MPs) such as polystyrene (PS), polyvinylchloride (PVC), polyurethane (PU), polymethyl methacrylate (PMMA), polyamide (PA), polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), polychloropene (PCP) and polycarbonate (PC) on the aquatic organism (zebrafish). The toxicity was evaluated based on the docking of the MPs on cytochrome P450 (CYP P450) protein crystals. The binding affinities (ΔG) followed the order, PC (-6.9 kcal/mol) > PET (-6.1 kcal/mol) > PP (-5.8 kcal/mol) > PA (-5.6 kcal/mol) > PS (-5.1 kcal/mol) > PU (-4.1 kcal/mol) > PMMA (-3.9 kcal/mol) > PCP (-3.3 kcal/mol) > PVC (-2.4 kcal/mol) > PE (-2.1 kcal/mol). The primary driving factors for the binding of the MPs and the protein were hydrophobic force, and hydrogen bonding based on the molecular dynamics analysis and surrounding amino acid residues. Furthermore, a 210-5 fractional factorial design method was estimated to identify the main effect and second-order effects of MPs in a composite contamination system on binding affinity/energy to CYP450 receptor protein of zebrafish, combined with a fixed effects model. The findings showed that different MPs combinations had varying impacts on aquatic toxicity; as a consequence, the best combination of MPs with the lowest aquatic toxicity effect could be excluded. The factorial designs showed that the PU-PS and PP-PA combination and single PCP, has the most significant main effect on CYP450 receptor protein of zebrafish which translates to an optimum toxicity level of -4.61 kcal/mol. The investigation offers a theoretical foundation for identifying the hazardous impacts of MPs on aquatic life.