Lycium barbarum polysaccharides alleviate PVC microplastic-induced ferroptosis and fibrosis in duck kidneys by attenuating NCOA4-mediated ferritinophagy: an in vivo study.

Microplastics (MPs) contamination is widespread and continues to increase. Compared to terrestrial organisms, mallards as waterfowl are more susceptible to MPs exposure. Lycium barbarum polysaccharides (LBP) are bioactive compounds extracted from goji berries; however, the mechanism by which LBP alleviates polyvinyl chloride microplastics (PVC-MPs)-induced renal damage in ducks remains unknown. In this study, network pharmacology was utilized to identify target proteins of LBP against PVC-MPs-induced renal injury. Analyses of protein-protein interaction (PPI) networks, drug-disease-target networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment identified 107 key targets, with core targets predominantly enriched in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Male mallard ducks were divided into four groups: control, PVC-MPs (10 mg/kg in diet), LBP (50 mg/kg gavage), and PVC‑MPs + LBP. Our results indicate that PVC-MPs significantly reduced kidney weight and organ coefficient while elevating renal injury biomarkers. PVC-MPs also induced pathological damage and interstitial fibrosis, disrupted redox homeostasis (characterized by increased MDA and decreased GSH/CAT), and suppressed the NRF2/Kelch-like ECH-associated protein 1 (KEAP1) pathway. Furthermore, PVC-MPs caused renal iron accumulation and ferroptosis (reduced GPX4 and FTH1, increased ACSL4), along with activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy (elevated LC3, ATG5, NCOA4, and autophagosome formation). Notably, LBP treatment significantly reversed all these effects. In conclusion, LBP alleviates PVC-MPs-induced renal ferroptosis and fibrosis by attenuating NCOA4-mediated ferritinophagy. This study provides novel insights into the nephrotoxic mechanisms of PVC-MPs and supports the development of LBP as a protective feed additive in poultry farming.