Rutin Ameliorates Cadmium-Induced Necroptosis in the Chicken Liver via Inhibiting Oxidative Stress and MAPK/NF-κB Pathway.

Cadmium (Cd) is a recognized toxic metal and exerts serious hepatotoxicity in animals and humans. Rutin (RUT) is a dietary bioflavonoid with strong antioxidant and anti-inflammatory potential. However, little is known about the alleviating effect of RUT against Cd-induced liver necroptosis. The aim of this study was to ascertain the ameliorative mechanism of RUT on necroptosis triggered by Cd in chicken liver. One hundred twenty-eight 100-day-old Isa hens were randomly divided into four groups: the control group, RUT group, Cd + RUT cotreated group, and Cd group. Cd exposure prominently elevated Cd accumulation and the activities of liver function indicators (ALT and AST). Furthermore, the histopathological results, the overexpression of genes (RIPK1, RIPK3, and MLKL) related to the necroptosis pathway, and low Caspase 8 levels in Cd-exposed chicken liver indicated that Cd intoxication induced necroptosis in chicken liver. Meanwhile, Cd administration drastically increased the levels of oxidizing stress biomarkers (ROS production, MDA content, iNOS activity, and NO generation), and obviously reduced the activities of antioxidant enzymes (SOD, GPx, and CAT) and total antioxidant capacity (T-AOC) in chicken liver. Cd treatment promoted the expression of the main members of the MAPK and NF-κB pathways (JNK, ERK, P38, NF-κB, and TNF-α) and activated heat shock proteins (HSP27, HSP40, HSP60, HSP70, and HSP90). However, RUT application remarkably alleviated these Cd-induced variations and necroptosis injury. Overall, our study demonstrated that RUT might prevent Cd-induced necroptosis in the chicken liver by inhibiting oxidative stress and MAPK/NF-κB pathway.