Nephrotoxicity and possible mechanisms of decabrominated diphenyl ethers (BDE-209) exposure to kidney in broilers.

Abstract

The flame retardant decabrominated diphenyl ether (BDE-209) is a widely used chemical in a variety of products and exists extensively in the environment. BDE-209 has been reported to induce kidney injury and dysfunction. However, the causes and mechanisms of its nephrotoxicity are still under investigation. In this study, 150 male broilers were exposed to BDE-209 concentrations of 0, 0.004, 0.04, 0.4, 4.0\xa0g/kg for 42 days. The relative kidney weight, histopathology, markers of renal injury, oxidative stress, inflammation, apoptosis and the expression of MAPK signaling pathways-related proteins were assessed. The results showed that the concentrations of blood urea nitrogen (BUN), creatinine (CRE) and the neutrophil gelatinase-associated lipocalin (NGAL), significantly increased after exposure to BDE-209 with the doses more than 0.04\xa0g/kg. Similarly, severe damage of renal morphology was observed, including atrophy and necrosis of glomeruli, and swelling and granular degeneration of the renal tubular epithelium. In the renal homogenates, the oxidative stress was evidenced by the elevated concentrations of MDA and NO, and decreased levels of GSH-Px, GSH and SOD. Due to the inflammatory response, the level of NF-κB and the pro-inflammatory cytokines TNF-α, IL-1β, IL-18 were remarkably upregulated, while the content of the anti-inflammatory cytokine IL-10 decreased. Additionally, the apoptotic analysis showed notable upregulations of Bax/Bcl-2 ratio, the relative expression of p-ERK1/2 and p-JNK1/2, and the expression of Bax, cytochrome c and caspase 3. The present study indicates that BDE-209 exposure can cause nephrotoxicity in broilers through oxidative stress and inflammation, which activate the phosphorylation of key proteins of the MAPK signaling pathways, and subsequently induce mitochondria-mediated kidney apoptosis.