Abstract: The aim of this experiment was to study the effect of ferroptosis on cadmium-induced liver damage of chicken. After 7 d pre-feeding, thirty 1-day-old Hylan white chickens were randomly divided into control group (group C) and cadmium exposure test group (group Cd), with 15 chickens in each group. Chickens in group C were fed the basal diet, and chickens in group Cd were fed the diet supplemented with 140 mg·kg^-1 CdCl₂. Samples were taken at 20, 40 and 60 d after cadmium exposure to observe liver histopathological and ultra-pathological changes, and to detect liver functional enzyme activities, levels of inflammatory factors, oxidative stress, ferroptosis-related factors and mitochondrial fusion-related factors in the liver. Based on the establishment of liver cancer cell line (LMH) exposed to cadmium, groups of iron death activator and iron death inhibitor were put up as well, and the cell activity, expression of inflammatory factors, iron death related factors and mitochondrial fusion related factors were detected after 24 hours. The results showed that the activity of liver functional enzymes in the serum of chickens in the group Cd was significantly increased; Liver cells were disorder, vacuolar degeneration or even necrosis; Liver congestion, serousand fibrinous exudation, and inflammatory cell infiltration; The relative expression levels of inflammatory factors LOX, NF-κB, TNF-α, IL-6 and IL-1β mRNA in the liver were up-regulated, and the contents of TNF-α, IL-6 and IL-1β were increased; The content of peroxide MDA was significantly increased, the activities of antioxidant enzymes GSH-Px and SOD were significantly decreased; The relative expression levels of ferroptosis metabolism-related factors FTH1 and TFR mRNA were significantly increased levels. The expression levels of GPX4 was significantly decreased, and the expression levels of ACSL4 and PTGS2 were extremely significantly increased; Mitochondrial fusion-related factors OPA1, Mfn1/2 mRNA expression levels were significantly decreased. Cadmium exposure and ferroptosis activators can both induce ferroptosis in LMH cells, promote the release of inflammatory factors, cause mitochondrial dysfunction, and lead to cell damage; Ferroptosis inhibitor significantly inhibited the cadmium-induced release of inflammatory factors and mitochondrial damage in LMH cells, and alleviated the decrease in cell viability caused by cadmium. The results indicated that cadmium exposure caused the accumulation of lipid peroxides, the disturbance of iron metabolism, and ferroptosis, which eventually promoted inflammatory damage to the liver.

Key words: cadmium, ferroptosis, liver damage, chickens