Copper (Cu) is an essential trace element that plays a crucial role in numerous physiopathological processes related to human and animal health. In the poultry industry, Cu is used to promote growth as a feed supplement, but excessive use can lead to toxicity on animals. Cytochrome P450 enzymes (CYP450s) are a superfamily of proteins that require heme as a cofactor and are essential for the metabolism of xenobiotic compounds. The purpose of this study was to explore the influence of exposure to Cu on CYP450s activity and apoptosis in the jejunum of broilers. Hence, we first simulated the Cu exposure model by feeding chickens diets containing different amounts of Cu. In the present study, histopathological observations have revealed morphological damage to the jejunum. The expression levels of genes and proteins of intestinal barrier markers were prominently downregulated. While the mRNA expression level of the gene associated with CYP450s was significantly increased. Additionally, apoptosis-related genes and proteins (Bak1, Bax, Caspase-9, Caspase-3, and CytC) were also significantly augmented by excessive Cu, while simultaneously decreasing the expression of Bcl-2. It can be concluded that long-term Cu exposure affects CYP450s activity, disrupts intestinal barrier function, and causes apoptosis in broilers that ultimately leads to jejunum damage.

Graphical Abstract

中文翻译：

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长期铜暴露会改变肉鸡 CYP450 活性并诱导空肠损伤和细胞凋亡

铜 (Cu) 是一种必需的微量元素，在与人类和动物健康相关的众多生理病理过程中发挥着至关重要的作用。在家禽业中，铜被用作饲料补充剂来促进生长，但过量使用会对动物产生毒性。细胞色素 P450 酶 (CYP450) 是一个蛋白质超家族，需要血红素作为辅助因子，对于外源化合物的代谢至关重要。本研究的目的是探讨Cu暴露对肉鸡空肠CYP450s活性和细胞凋亡的影响。因此，我们首先通过饲喂含有不同铜含量的鸡饲料来模拟铜暴露模型。在本研究中，组织病理学观察揭示了空肠的形态学损伤。肠道屏障标志物基因和蛋白的表达水平显着下调。而CYP450s相关基因的mRNA表达水平显着增加。此外，过量的 Cu 也会显着增强凋亡相关基因和蛋白（Bak1、Bax、Caspase-9、Caspase-3 和 CytC），同时降低 Bcl-2 的表达。可以得出结论，长期接触铜会影响CYP450s活性，破坏肠道屏障功能，并引起肉鸡细胞凋亡，最终导致空肠损伤。

图形概要