Copper exposure promotes ferroptosis of chicken (Gallus gallus) kidney cells and causes kidney injury

Mengran Wang; Feiyang Ma; Gaolong Zhong; Tingyu Liang; Bingxia Sun; Jianzhao Liao; Lianmei Hu; Jiaqiang Pan; Zhaoxin Tang

doi:10.1016/j.jtemb.2024.127501

Copper exposure promotes ferroptosis of chicken (Gallus gallus) kidney cells and causes kidney injury

J Trace Elem Med Biol. 2024 Jul 23:86:127501. doi: 10.1016/j.jtemb.2024.127501. Online ahead of print.

Authors

Mengran Wang¹, Feiyang Ma², Gaolong Zhong³, Tingyu Liang⁴, Bingxia Sun⁵, Jianzhao Liao⁶, Lianmei Hu⁷, Jiaqiang Pan⁸, Zhaoxin Tang⁹

Affiliations

¹ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: wangmengran@stu.scau.edu.cn.
² College of Animal Science, Anhui Science and Technology University, Chuzhou, Anhui 233100, China. Electronic address: mfy@ahstu.edu.cn.
³ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: zgl1216@stu.scau.edu.cn.
⁴ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: 13713821698@163.com.
⁵ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: sunbingxia@stu.scau.edu.cn.
⁶ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: liaojz@stu.scau.edu.cn.
⁷ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: hulianmei@scau.edu.cn.
⁸ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: panjq@scau.edu.cn.
⁹ College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong 510642, China. Electronic address: tangzx@scau.edu.cn.

PMID: 39053339
DOI: 10.1016/j.jtemb.2024.127501

Abstract

Purpose: While copper (Cu) is essential for biological organisms, excessive Cu can be harmful. Ferroptosis is a programmed cell death pathway, but the role of ferroptosis in renal injury induced by Cu is limited. The aim of this study was to investigate the role of ferroptosis in kidney injury in chickens and the molecular mechanism by which Cu promotes renal ferroptosis.

Materials and methods: Chicken were subjected to Cu treatment by artificially adding excess Cu to the basal diet (the Cu concentration in the diet was supplemented to 110-330 mg/kg), and the impact on kidney fibrosis, tissue structure, and ferroptosis-related molecular markers was studied. Then, the expression levels of genes and proteins related to ferroptosis, iron metabolism and ferroautophagy were detected to explore the promoting effect of Cu on ferroptosis in chicken kidney.

Main findings: Cu treatment resulted in significant fibrosis and tissue structure damage in chicken kidneys. Molecular analysis revealed a significant upregulation of LC3Ⅱ, P62, ATG5, and NCOA4, along with a decrease in FTH1 and FTL protein levels. Additionally, crucial markers of ferroptosis, including the loss of GPX4, SLC7A11, and FSP1, and an increase in PTGS2 and ACSL4 protein levels, were observed in chicken kidneys after Cu exposure.

Conclusion: Our study showed that dietary Cu excess caused kidney injury in brochickens and exhibited ferroptosis-related features, including lipid peroxidation, reduction of ferritin, and downregulation of FSP1 and GPX4. These results indicate that excess Cu can induce renal ferroptosis and lead to kidney injury in chickens. This study highlights the complex interplay between Cu ions and ferroptosis in the context of renal injury and provides a new perspective for understanding the mechanism of Cu-induced renal injury.

Keywords: Copper; Ferritinophagy; Ferroptosis; Iron metabolism; Kidney.