RESUMO
Cadmium is a highly toxic metal threatening human and animal health. N-acetyl-L-cysteine (NAC) was reported to play a positive role in disease treatment and immune regulation. The present study aimed to explore the effect of NAC administration on Cd-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages. Peritoneal macrophages isolated from Isa Brown male chickens were exposed to CdCl2 (20 or 50 µM) and/or NAC (500 µM) for different time periods. Results showed that Cd caused dose-dependent damage on chicken peritoneal macrophages characterized by morphologic and ultrastructural alterations, increased cell apoptosis, reactive oxygen species accumulation and mitochondrial injury. Cd exposure inhibited phagocytic activity of chicken peritoneal macrophages, and promoted transcriptional status of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in both unactivated macrophages and cells in response to lipopolysaccharide (LPS) stimuli. Pretreatment with 500 µM NAC did not affect growth of normal chicken peritoneal macrophages, while remarkably inhibiting Cd-caused cell death, oxidative stress, and mitochondrial membrane depolarization. NAC pretreatment significantly prevented intracellular Cd2+ accumulation in the Cd-exposed macrophages. Inhibitory effects of NAC on Cd-induced ROS accumulation and mitochondrial injury on chicken macrophages were confirmed in HD-11 macrophage cell line. In addition, NAC pretreatment promoted the phagocytic activity of Cd-exposed chicken peritoneal macrophages, and significantly inhibited expression of pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) in both Cd-exposed macrophages and Cd-treated cells in response to LPS stimuli. In conclusion, the present study firstly demonstrated the antagonistic effect of NAC against Cd-caused damage and abnormal immune response on chicken peritoneal macrophages. Protective effect of NAC on chicken macrophages was highly related to its suppression on Cd-induced ROS overproduction, pro-inflammatory reaction and intracellular Cd2+ accumulation.