Cadmium exposure induces necroptosis of porcine spleen via ROS-mediated activation of STAT1/RIPK3 signaling pathway

Cadmium (Cd), a heavy metal, is used in a wide range of applications, such as plastics, electroplating process, electronics, and so forth. Due to its bioaccumulation ability, Cd can contaminate soil, water, air and food. To determine the effect of Cd exposure on the necroptosis in pig spleen and its mechanistic investigation, we constructed a model in pigs by feeding them food containing 20 mg/kg Cd. In this study, we analyzed the effects of Cd exposure on pig spleen through HE staining, Quantitative real-time PCR (qRT-PCR), Western blot (WB), and principal component analysis (PCA). Results show that Cd exposure can destroy the structure and function of pig spleen, which is closely related to necroptosis. Further results show that Cd exposure can induce necroptosis through ROS-mediated activation of Signal transducer and activator of transcription 1/Receptor-Interacting Serine/Threonine-Protein Kinase 3 (STAT1/RIPK3) signaling pathway in pig spleen. Additionally, Cd exposure also can affect the stability of mitochondrial-associated endoplasmic reticulum membrane (MAMs) structure, which also contributes to the process of necroptosis. Our study provides insights into the physiological toxicity caused by Cd exposure.

Automated summary

In this study, a model was constructed in pigs by feeding them food containing 20 mg/kg Cd to determine the effect of Cd exposure on necroptosis in pig spleen. Results showed that Cd exposure can destruct the structure and function of pig spleen, which is closely related to necroptosis. Furthermore, Cd exposure can induce necroptosis through ROS-mediated activation of the STAT1/RIPK3 signaling pathway in pig spleen, and it can also affect the stability of MAMs structure, which contributes to the process of necroptosis.