A new insight into the mechanism of cadmium-induced nephrotoxicity and antagonism of selenium nanoparticles: modulation of MTF1-MT axis dependent metal homeostasis.

Cadmium (Cd) is a highly toxic pollutant that causes direct harm to the kidney. Cellular metal homeostasis is one of the key targets of heavy metal toxicity and may represent an alleviation pathway for environmentally-related kidney disease. Selenium nanoparticles (SeNPs) is a antioxidant and is considered to be involved in the regulation of cellular metal transport. However, the impact of Cd on renal metal homeostasis and the protective role of SeNPs against Cd-induced nephrotoxicity have not been fully elucidated. Chickens were treated with CdCl and SeNPs during this 90-day trial. SeNPs alleviated Cd-induced kidney injury, preserved filter barrier, and restored disrupted metal transport and selenoprotein biosynthesis, thereby normalizing the renal Cd, Se, Zn, Fe, and Cu levels. Further investigation identified that SeNPs increased nuclear translocation of MTF1 and the transcription of downstream genes MT1 and MT2. JNK activated MTF1 under a low dose of Cd exposure in response to metal stress. However, high doses of Cd exposure led to MTF1 dysfunction and Cd accumulation. Interestingly, SeNPs upregulated MTF1 expression despite down-regulation of JNK phosphorylation, suggesting that SeNPs activated the MTF1-MT axis in a non-JNK-dependent pathway. These results support the key role of SeNPs in responding to metal stress.