The impact of copper-induced oxidative damage on the endoplasmic reticulum quality control system in broiler kidneys

Copper (Cu) is a pervasive element utilized in economic animal production. However, overuse can have toxic effects on animals and threaten public food safety. To gain a deeper understanding of the mechanisms underlying Cu-induced nephrotoxicity, an in-depth analysis was conducted on the effects of Cu on the renal endoplasmic reticulum quality control (ERQC) system. In the course of this experiment, one-day-old chicks were fed diets comprising Cu levels (11, 110, 220 and 330 mg/kg) for 49 days. Our findings indicate that an excess of Cu may result in oxidative stress, which may then induce tissue damage within the kidney. Furthermore, the experimental results indicated that elevated Cu levels may disrupt to the ERQC system in chicken kidneys. The mRNA levels of GRP78, GRP94, ATF4, IRE1, and XBP1, as well as the protein levels of GRP78, GRP94, IRE1, XBP1, and CHOP, were markedly elevated in all treatment groups relative to the control group. Conversely, the mRNA and protein levels of eIF2α and ATF6 exhibited a notable decline with the increase in Cu levels. Similarly, RTN3, ATL1, and ATL2 mRNA levels as well as RTN3 and ATL3 protein levels exhibited a notable elevation in conjunction with an appreciable decline in FAM134B and SEC62 mRNA and protein levels, respectively, as Cu levels increased. Furthermore, bioinformatics analyses indicated a correlation between oxidative damage and ERQC markers. The above results suggest that Cu-induced oxidative damage may injure to chicken kidneys via disturbances in the ERQC system.