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氟氰戊菊酯通过调节细胞色素 P450 酶系统和抑制 Nrf2/HO-1 通路诱导鸡心脏损伤。

Lambda-cyhalothrin induces heart injury in chickens by regulating cytochrome P450 enzyme system and inhibiting Nrf2/HO-1 pathway.

机构信息

College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China.

College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China; Key Laboratory of Chicken Genetics and Breeding, Ministry of Agriculture and Rural Affairs, Harbin, Heilongjiang 150030, PR China.

出版信息

Poult Sci. 2024 Oct;103(10):104154. doi: 10.1016/j.psj.2024.104154. Epub 2024 Aug 2.

Abstract

Lambda-cyhalothrin (LCT) is a common pyrethroid insecticide widely used for ectoparasite control and hygiene pest prevention in poultry and this study aimed to investigate the mechanisms of LCT-induced cardiac injury in chickens. Low, medium, and high-dose LCT exposure models in chickens were established and hematoxylin and eosin (H&E) staining, dihydroethidium (DHE) staining, TUNEL staining, immunofluorescence, biochemical analysis, and gene expression analysis were used to study the effects of LCT exposure on the chicken heart. The results showed that LCT exposure increased the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH), led to muscle fiber breakage and inflammatory cell infiltration and caused cardiac tissue damage. The DHE staining and biochemical analysis revealed that LCT exposure resulted in the excessive accumulation of ROS, decreased activities/levels of catalase (CAT), total superoxide dismutase (T-SOD), and glutathione (GSH), and increased levels of the oxidative damage marker malondialdehyde (MDA). The TUNEL staining indicated that LCT exposure increased apoptosis possibly through the elevated expression of pro-apoptotic genes in the mitochondrial pathway, the reduced expression of anti-apoptotic genes, the upregulation of pro-inflammatory factors and the downregulation of anti-inflammatory factors. Here, LCT exposure significantly inhibited the expression of genes in the Nrf2/HO-1 pathway and activated the expression of genes in the CYP450 enzyme system. Compared to the low-dose group, the high-dose LCT exposure group showed lower levels of apoptosis and inflammation, possibly related to the low oxidative stress levels mediated by the decreased expression of the CYP450 enzyme system. In conclusion, LCT exposure induces oxidative stress, apoptosis, and inflammation in chicken hearts, which may be associated with the inhibition of the Nrf2/HO-1 pathway and activation of the CYP450 enzyme system. This study provides a theoretical basis for the safer use of insecticides in poultry production.

摘要

氯氟氰菊酯(LCT)是一种常见的拟除虫菊酯类杀虫剂,广泛用于家禽的寄生虫控制和卫生害虫防治。本研究旨在探讨 LCT 诱导鸡心脏损伤的机制。建立了低、中、高剂量 LCT 暴露模型,通过苏木精和伊红(H&E)染色、二氢乙锭(DHE)染色、TUNEL 染色、免疫荧光、生化分析和基因表达分析研究了 LCT 暴露对鸡心脏的影响。结果表明,LCT 暴露增加了血清肌酸激酶(CK)和乳酸脱氢酶(LDH)水平,导致肌纤维断裂和炎性细胞浸润,引起心肌组织损伤。DHE 染色和生化分析显示,LCT 暴露导致 ROS 过度积累,CAT、总超氧化物歧化酶(T-SOD)和谷胱甘肽(GSH)活性/水平降低,氧化损伤标志物丙二醛(MDA)水平升高。TUNEL 染色表明,LCT 暴露可能通过增加线粒体途径中促凋亡基因的表达、降低抗凋亡基因的表达、上调促炎因子和下调抗炎因子来增加细胞凋亡。在此,LCT 暴露显著抑制了 Nrf2/HO-1 通路基因的表达,激活了 CYP450 酶系统基因的表达。与低剂量组相比,高剂量 LCT 暴露组的细胞凋亡和炎症水平较低,这可能与 CYP450 酶系统表达降低介导的氧化应激水平降低有关。总之,LCT 暴露诱导鸡心脏氧化应激、细胞凋亡和炎症,这可能与 Nrf2/HO-1 通路的抑制和 CYP450 酶系统的激活有关。本研究为家禽生产中更安全地使用杀虫剂提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/707e/11372963/da2bbdec3255/gr4.jpg

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