In vitro protective effects of cyanidin-3-O-glucoside against toxicity induced by continuous exposure to antimony(III) in intestinal epithelial cells

Antimony (Sb), a heavy metal employed in PET manufacturing, is an emerging contaminant due to its ability to leach into food and beverages. Chronic exposure can impair intestinal health by disrupting epithelial barrier functionality and promoting oxidative stress, inflammation, and apoptosis. This study investigated the protective effects of cyanidin-3-O-glucoside (C3G), a dietary anthocyanin, against continuous exposure to low concentrations of Sb(III) during intestinal epithelial Caco-2 cell differentiation. C3G (20-40 μM) attenuated barrier dysfunction, increasing TEER values and reducing fluorescein permeability, and reduced reactive oxygen species, mitigating inflammatory responses by inhibiting NF-κB activation and downregulating IL-6 and COX-2 expression. C3G alleviated endoplasmic reticulum (ER) stress, decreasing eIF2α phosphorylation and ATF4 and CHOP expression. Furthermore, it reduced apoptosis, as shown by lower caspase-3 activation, and displayed antioxidant activity, partly mediated by the Nrf2‑related pathway. Overall, C3G protects intestinal epithelial function from Sb-induced stress by modulating oxidative, inflammatory, ER stress, and apoptotic pathways.