Hepatotoxicity evaluation and possible mechanisms of decabrominated diphenyl ethers (BDE-209) in broilers: Oxidative stress, inflammatory, and transcriptomics

Abstract

Decabrominated diphenyl ether (BDE-209), a persistent organic pollutant, is linked to a great number of health problems, the most severe of which impact the liver due to its role in the elimination and degradation of exogenous harmful substances. Though the hepatotoxicity of BDE-209 has been observed, its underlying mechanism is yet unknown. The purpose of this study is to thoroughly investigate the hepatotoxicity of BDE-209 and its molecular processes in broilers by subjecting 120 male broilers to varied concentrations of BDE-209 for 42 days. We observed that the bioaccumulation of BDE-209 in the liver in a dose-dependent manner, and that BDE-209 exposure can raise the concentrations of ALT, AST, and GGT, accompanied by hepatocyte fatty degeneration and inflammatory foci. In the hepatic homogenates, oxidative stress was evidenced by elevated levels of MDA and ROS and decreased activies of SOD and CAT. Additionally, pro-inflammatory cytokines including IL-1, IL-1β, TNF-α, IL-8 levels were increased, whereas anti-inflammatory cytokine IL-4 level was declined. Furthermore, RNA sequencing revealed that genes involved in inflammation were considerably dysregulated, and real-time PCR verified the expressed alterations of numerous genes related to the MAPK and WNT signaling pathways. The protein concentrations of NF-κB, β-catenin, and WNT5A, and the phosphorylation levels of JNK and ERK were all dramatically enhanced. The current study indicates that BDE-209 exposure can cause hepatotoxicity in broilers via bioaccumulation and oxidative stress, which then activates the MAPK and WNT signaling pathways, subsequently generating inflammation and hepatic injury.