Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway

• Main Authors: Chang Liu, Yaohui Zhu, Zhenxiang Lu, Weina Guo, Bayaer Tumen, Yalan He, Chao Chen, Shanshan Hu, Kangzhi Xu, Yan Wang, Lei Li, Shenghe Li
• Format: Article
• Language: English
• Published: MDPI AG 2019-12-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: cadmium; acute liver injury; nrf2; nlrp3; nf-κb; mapks
• Online Access: https://www.mdpi.com/1660-4601/17/1/138
• ISSN: 1660-4601

Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.