The Alleviative Effects of Quercetin on Cadmium-Induced Necroptosis via Inhibition ROS/iNOS/NF-κB Pathway in the Chicken Brain.

Cadmium (Cd), a ubiquitous environmental pollutant, has neurotoxicity to humans and animals. Quercetin (QE), the main component of flavonoids, has strong antioxidant and anti-inflammatory effects. However, little is reported about the influence of Cd exposure on necroptosis in the chicken brain and the antagonistic impacts of QE against Cd-induced brain necroptosis. The aim of this study was to ascertain the alleviative mechanism of QE on Cd-induced necroptosis in the chicken brain. Two hundred 3.5-month-old Isa hens were randomly divided into four groups, control group, QE group, Cd group, and Cd + QE co-administration group. The histopathological analysis indicated that necrosis features were observed in the Cd-intoxicated chicken brains. Meanwhile, the expression levels of RIPK1, RIPK3, and MLKL were elevated and the level of Caspase 8 was reduced in the Cd group, which further testified Cd triggered the occurrence of necroptosis in the chicken brain. Cd exposure obviously increased Cd accumulation, ROS generation, and MDA level; weakened the activities of antioxidase (SOD, GPx, and CAT); enhanced iNOS activity and NO production; promoted the expression of inflammatory factors (NF-κB, TNFα, COX-2, iNOS, PTGEs, and IL-1β); and activated HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90). But, these Cd-caused variations were obviously attenuated in the Cd + QE group. This study indicated that QE had an alleviative effect on Cd-induced necroptosis in the chicken brain through inhibition ROS/iNOS/NF-κB pathway.