Fucoidan Protects Against Cadmium-Induced Cytotoxicity in PK-15 Cells by Restoring Autophagic Flux: Involvement of the TFEB Signaling Pathway

Cadmium (Cd) is a persistent environmental pollutant that poses a significant health risk to humans and animals, with acute exposure known to induce kidney injury. Fucoidan (Fc), a natural bioactive polysaccharide derived from brown algae, exhibits diverse biological activities; however, its potential to protect against Cd-induced kidney damage and the underlying mechanisms remain unclear. In this study, we investigated the effects of Fc on Cd-induced renal injury in vitro and further explored the role of transcription factor EB (TFEB) in regulating autophagy in its protective mechanism. Our results demonstrate that in Cd-exposed porcine kidney cells (PK-15), Fc suppressed the expression of renal inflammatory factors (TNF-α, IL-1β) and kidney injury markers (NGAL, NTN-1, KIM-1), reduced reactive oxygen species (ROS) production, and downregulated apoptosis-related proteins (cleaved caspase-3 and cleaved caspase-9). Mechanistically, Fc upregulated TFEB protein expression, enhanced the levels of lysosomal function-related proteins (Cathepsin B, CTSB; Cathepsin D, CTSD), and reversed Cd-induced autophagic flux blockade. Importantly, TFEB silencing abolished the protective effects of Fc. Collectively, these findings suggest that Fc exerts renoprotective effects against Cd-induced injury by restoring autophagic flux, a process that involves TFEB. Keywords: fucoidan; cadmium; autophagy; TFEB