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

Int J Environ Res Public Health. 2019 Dec 24;17(1):138. doi: 10.3390/ijerph17010138.

Abstract

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.

Keywords: Cadmium; MAPKs; NF-κB; NLRP3; Nrf2; acute liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium / toxicity*
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / physiopathology*
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Animal
  • NF-E2-Related Factor 2 / drug effects
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / drug effects
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*

Substances

  • NF-E2-Related Factor 2
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Cadmium
  • Mitogen-Activated Protein Kinases