1. Academic Validation
  2. CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses

CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses

  • Arch Toxicol. 2022 Nov;96(11):2913-2926. doi: 10.1007/s00204-022-03357-4.
Liqiang Jiang  # 1 Wei Liu  # 1 Jingnan Xu 1 Xinxin Gao 1 Haiguang Zhao 1 Shurou Li 1 Wenlong Huang 1 Zhengtao Yang 1 Zhengkai Wei 2
Affiliations

Affiliations

  • 1 College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, People's Republic of China.
  • 2 College of Life Sciences and Engineering, Foshan University, Foshan, 528225, Guangdong Province, People's Republic of China. [email protected].
  • # Contributed equally.
Abstract

With the widespread use of copper oxide nanoparticles (CuO-NPs), their potential toxicity to the environment and biological health has attracted close attention. Heterophil extracellular traps (HETs) are an innate immune mechanism of chicken heterophils against adverse stimuli, but excessive HETs cause damage. Here, we explored the effect and mechanism of CuO-NPs on HETs formation in vitro and further evaluated the potential role of HETs in chicken liver and kidney injury. Heterophils were exposed to 5, 10, and 20 µg/mL of CuO-NPs for 2 h. The results showed that CuO-NPs induced typical HETs formation, which was dependent on NADPH Oxidase, P38 and extracellular regulated protein kinases (ERK1/2) pathways, and glycolysis. In in vivo experiments, fluorescence microplate and morphological analysis showed that CuO-NPs elevated the level of HETs in chicken serum and caused liver and kidney damage. Meanwhile, CuO-NPs caused hepatic oxidative stress (MDA, SOD, CAT, and GSH-PX imbalance), and also induced an increase in mRNA expression of their inflammatory and apoptosis-related factors (IL-1β, IL-6, TNF-α, COX-2, iNOS, NLRP3, and Caspase-1, 3, 11). However, these results were significantly altered by DNase I (HETs degradation reagent). In conclusion, the present study demonstrates for the first time that CuO-NPs induce the formation of HETs and that HETs exacerbate pathological damage in chicken liver and kidney by promoting oxidative stress and inflammation, providing insights into immunotoxicity and potential prevention and treatment targets caused by CuO-NPs overexposure.

Keywords

Chicken; CuO-NPs; Heterophile extracellular traps; Liver damage; Oxidative stress.

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