Effect of hesperidin on nanocopper induced PANoptosis in chicken kidney through RIPK1/ZBP1 pathway

Recently, nanomaterials, such as nano-copper (nano-Cu), have become increasingly prevalent in daily life due to their excellent properties such as antibiotics and tumor therapy. However, the potential harm of nano-copper to organisms and the environment cannot be ignored. Hesperidin (Hes) is a flavonoid substance that exists in citrus plants, which has beneficial functions for organisms such as anti-oxidation and anti-inflammation. Nevertheless, whether hesperidin can alleviate nano-copper-induced renal toxic injury, especially renal PANoptosis (a complex form of programmed cell death regulated by the PANoptosome) induced by nano-copper, is still unclear. Therefore, the 120 chickens were randomly assigned to four groups: Control group, nano Cu group (300 mg/kg), nano Cu + Hes group (nano-Cu, 300 mg/kg; Hes, 150 mg/kg), and Hes group (150 mg/kg). The findings showed that nano-copper could induce toxic damage to the chicken kidney, causing structural damage to glomeruli and renal tubules, renal hemorrhage and increased fibrosis, and induce PANoptosis. Genes and proteins related to PANoptosis (pyroptosis: NLRP3, ASC, Caspase-1; apoptosis: FADD, Caspase-8, Caspase-9; necroptosis: RIPK1, MLKL, ZBP1) expression levels were significantly increased. Our results found that Hes could alleviate nephrotoxicity induced by nano-copper and inhibit PANoptosis in the kidney. The findings could contribute to a better understanding of nephrotoxicity induced by nano-copper and the underlying therapeutic action of hesperidin on nano-copper poisoning, which also established a foundation for further study of the toxic effects of nano-copper and the therapeutic effects of hesperidin.