Citrinin Induces Hepatic Inflammatory Injury through the PERK–CHOP–NLRP3 Axis-Mediated Pyroptosis

Citrinin (CTN), a widespread food and feed contaminant, poses a significant health risk, yet its hepatic toxicity remains unclear. Here, we investigated the role of endoplasmic reticulum (ER) stress-mediated pyroptosis in CTN-induced liver injury using mice and HL-7702 cells. CTN exposure disrupted the hepatic cord structure, induced hepatocyte swelling with karyolysis, and promoted inflammatory infiltration. Liver injury markers and pro-inflammatory cytokines IL-1β and IL-18 were significantly elevated in both models, confirming inflammatory liver injury. Mechanistically, CTN activated pyroptosis-related proteins and triggered ER stress. In HL-7702 cells, CTN-induced inflammatory injury was mediated by NLRP3-dependent pyroptosis. Silencing CHOP alleviated injury by suppressing NLRP3 activation, while selective inhibition of PERK reduced CHOP expression and further attenuated pyroptosis. Collectively, these findings demonstrate that the PERK–CHOP pathway regulates NLRP3-dependent pyroptosis, contributing to CTN-induced hepatotoxicity. The PERK–CHOP–NLRP3 axis may represent a potential therapeutic target against CTN-related liver injury.