College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Pestic Biochem Physiol. 2023 Nov;196:105624. doi: 10.1016/j.pestbp.2023.105624. Epub 2023 Sep 16.
Chlorpyrifos (CPF), a widely used organophosphate pesticide that has caused large-scale contamination globally, has become a major concern. Baicalein (BAI), as a flavonoid extract, shows anti-inflammatory as well as antioxidant activities. The kidneys of fish serve to excrete toxins and are major target organs for environmental contaminants. However, it is not obvious whether BAI can counteract the damage caused by CPF exposure to fish kidneys. Therefore, we conducted a 30-day simulation of CPF poisoning and/or BAI treatment by adding 23.2 μg/L CPF to water and/or 0.15 g/kg BAI to feed. In the transmission electron microscopy results, we observed obvious phenomenon of autophagy and apoptosis in the CPF group, and the TUNEL staining and immunofluorescence of LC3B and p62 double-staining results confirmed that CPF induced autophagy and apoptosis in the kidney of common carp. Furthermore, CPF induced the increase of ROS level and inhibition of PI3K and Nrf2 pathways, which in turn triggered oxidative stress, autophagy and apoptosis in carp kidney according to western blot, RT-qPCR and kit assays. However, addition of BAI significantly alleviated oxidative stress, autophagy and apoptosis due to binding to PI3K protein. Additionally, through phylogenetic tree and structural domain analyses, we also found that the binding sites of BAI and PI3K are conserved in a variety of representative species. These results suggest that BAI antagonizes CPF-caused renal impairments in carp involving the PI3K/AKT pathway and the Nrf2 pathway. Our findings provide new insights into the nephrotoxicity effects of CPF and the potential use of BAI as a detoxification agent for CPF intoxication.
毒死蜱（CPF）是一种广泛使用的有机磷农药，已在全球范围内造成大规模污染，成为一个主要关注点。黄芩素（BAI）作为一种黄酮类提取物，具有抗炎和抗氧化活性。鱼类的肾脏用于排泄毒素，是环境污染物的主要靶器官。然而，BAI 是否可以抵消 CPF 暴露对鱼类肾脏造成的损害尚不清楚。因此，我们通过在水中添加 23.2μg/L CPF 和/或在饲料中添加 0.15g/kg BAI，进行了为期 30 天的 CPF 中毒和/或 BAI 处理模拟。在透射电子显微镜结果中，我们观察到 CPF 组中自噬和细胞凋亡的明显现象，TUNEL 染色和 LC3B 和 p62 双重免疫荧光染色结果证实 CPF 诱导了鲤鱼肾脏的自噬和细胞凋亡。此外，CPF 诱导 ROS 水平升高和 PI3K 和 Nrf2 途径抑制，进而根据 Western blot、RT-qPCR 和试剂盒测定，触发鲤鱼肾脏的氧化应激、自噬和细胞凋亡。然而，BAI 的添加通过与 PI3K 蛋白结合，显著减轻了氧化应激、自噬和细胞凋亡。此外，通过系统发生树和结构域分析，我们还发现 BAI 和 PI3K 的结合位点在各种代表性物种中是保守的。这些结果表明，BAI 通过 PI3K/AKT 途径和 Nrf2 途径拮抗 CPF 引起的鲤鱼肾脏损伤。我们的研究结果为 CPF 的肾毒性作用以及 BAI 作为 CPF 中毒解毒剂的潜在用途提供了新的见解。
