Keywords: 
• acrylonitrile /
• rats /
• spleen /
• oxidative stress /
• NF-κB

Abstract: To investigate the effect of acrylonitrile (ACN)-induced oxidative stress on nuclear transcription factor-κB (NF-κB) signaling pathway in rats spleen, 60 specific pathogen free (SPF) grade healthy adult male rats were randomly divided into 5 groups:control group (corn oil), low-, medium-, and high-dose groups (11.5, 23, 46 mg·kg^-1 ACN) and NAC groups (46 mg·kg^-1 ACN + 300 mg·kg^-1 NAC), and were treated once/day, 6 days/week, by intragastric gavage for 4 weeks. The spleen was isolated and weighed. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), the contents of glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in spleen were detected by spectrophotometry. The interleukin 6 (IL-6), interleukin 1β (IL^-1β), tumor necrosis factor-α (TNF-α) levels were determined by Elisa. The expressions of NF-κB, IκB and p-IκB were measured using western blotting and the expressions of NF-κB and IκB mRNA were determined by RT-qPCR. The results showed that the splenic wet weight of the rats were significantly decreased in the low- and middle-dose groups compared with the control group (P<0.05). The splenic coefficient was also significantly decreased in the middle-dose group (P<0.05). The contents of MDA in the spleen of rats were significantly increased in the medium- and high-dose groups (P<0.05) and the activities of SOD and GSH-Px were significantly increased in the high-dose group (P<0.05). The activity of CAT and the contents of T-AOC and GSH were all decreased in the low-dose group, whereas, the CAT activity was increased in the high-dose group (P<0.05). Meanwhile, the activities of SOD, CAT and GSH-Px and the contents of MDA, GSH and T-AOC were sig- nificantly decreased in the NAC group compared with the high-dose group (P<0.05). Compared with the control group, the contents of IL^-1β were decreased in the middle- and high-dose groups, and the levels of TNF-α were increased significantly in all dose groups (P<0.05). Compared with the high-dose group, the content of TNF-α was significantly decreased in the NAC group (P<0.05). Western Blot results showed that the expressions of NF-κB, IκB, and p-IκB were significantly increased in the medium- and high- dose groups compared with the control group (P<0.05). The expressions of IκB and p-IκB in NAC group was decreased in the high ACN group (P<0.05). RT-PCR results showed that the expression of NF-κB mRNA were increased in the low-, medium- and high-dose ACN groups compared with the control group (P<0.05). And the expressions of IκB mRNA were increased in the medium- and high-dose ACN groups compared with the control group (P<0.05). The expression of NF-κB mRNA was decreased in the NAC group compared with the high-dose group (P<0.05). Therefore, the present study sug- gests that subacute exposure to ACN could produce oxidative damage and immune system response in rats' spleen, and NAC might reduce the degree of injury through antagonism.