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

Chang Liu,Shanshan Hu,Weina Guo,Zhenxiang Lu,Yaohui Zhu,Yan Wang,Lei Li,Chao Chen,Yalan He,Kangzhi Xu,Bayaer Tumen,Shenghe Li

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.

Highlights

Cadmium (Cd) is a widespread industrial and environmental pollutant, which is has arisen from battery, metals smelting and refining, burning of chemical products, and cigarette smoking
Nod-like receptor 3 (NLRP3) is a critical molecular in inflammatory injury, we evaluated the expression of NLRP3 by western blotting
It was upregulated in the liver when the we evaluated the expression of NLRP3 by western blotting

Summary

Introduction

Cadmium (Cd) is a widespread industrial and environmental pollutant, which is has arisen from battery, metals smelting and refining, burning of chemical products, and cigarette smoking. Cd is a non-essential element that is found in the human body and that of animals. It can be absorbed into the body through the skin, respiratory passages, and digestive tract. Cd exposure can damage a wide variety of tissues, such as liver, kidney, lung, bone, and brain, and induce immune, nervous, and reproductive system injuries [2,3,4,5,6]. The liver is the largest gland of both the human and animal body and has multiple physiological functions, such as secretion of bile, participation in substance and energy metabolism, phagocytosis, detoxification, and defense. Cd exposure can lead to a variety of cancers, especially liver cancer [10]

Methods

Results

Discussion

Conclusion