Copper and vanadium induce oxidative stress and pyroptosis in the duck brain via activating the TLR4/NF-κB-p65 signaling pathway.

Abstract

Copper (Cu) and vanadium (V) are beneficial to the organizations as trace elements, but excessive intakes of Cu and V could damage the individual health with multi-organ injury, such as neurotoxicity. To estimate the combined effects of Cu and V on proptosis by the TLR4/NF-κB-p65 pathway in duck brains, a total of 72 ducks were divided into four groups: control group, Cu group (400 mg Cu/kg), V group (30 mg V/kg), and Cu + V group (400 mg Cu/kg + 30 mg V/kg) groups respectively. The results indicated that Cu and/or V could disrupt the trace element balance in the duck brain and caused nerve fiber disorders, neuronal vacuolization and mitochondrial destruction. Oxidative damage was observed in the brain, characterized by increased levels of MDA, NO, and LDH, and decreased levels of CAT, T-SOD, and GSH following exposure to Cu and/or V. Additionally, Cu and/or V triggered pyroptosis by upregulating the expression levels of pyroptosis-related factors (Caspase-1, NLRP3, NEK7, ASC, IL-18, IL-1β, GSDME, GSDMA, GSDMD) and enhancing the co-location puncta of Caspase-1 with GSDMD. Besides, Cu and/or V raised the expression levels of TLR4 and NF-κB-p65. Collectively, the results revealed that excess Cu or V induced oxidative stress and pyroptosis by activating the TLR4/NF-κB-p65 pathway in the duck brains, and the combined treatment of Cu and V aggravated the brain damage.