Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China.
School of Information Technology, Jiangxi University of Finance and Economics, No. 665 Yuping West street, Economic and Technological Development District, Nanchang 330032, Jiangxi, P. R. China.
Food Funct. 2022 Feb 21;13(4):2142-2154. doi: 10.1039/d1fo02855c.
Cadmium (Cd) and excessive molybdenum (Mo) have adverse impacts on animals. However, the hepatotoxicity co-induced by Cd and Mo in ducks has not been fully elucidated. In order to explore the impacts of Cd and Mo co-exposure on pyroptosis and apoptosis by the PTEN/PI3K/AKT pathway in the livers of ducks, 40 healthy 7-day-old Shaoxing ducks () were randomly assigned into 4 groups, and Cd or/and Mo were added to the basic diet per kilogram (kg): control group (0 mg Mo and 0 mg Cd), Mo group (100 mg Mo), Cd group (4 mg Cd), and Mo + Cd group (100 mg Mo and 4 mg Cd), with 16 weeks feed management. Results signified that Cd or/and Mo caused trace element imbalance, liver function and histomorphological abnormalities in the duck liver, and activated the PTEN/PI3K/AKT pathway through increasing PTEN mRNA and protein levels, reducing PI3K, AKT mRNA and p-AKT/AKT protein levels, which triggered pyroptosis and apoptosis increasing Caspase-1, NLRP3, NEK7, ASC, GSDME, GSDMA, IL-1β and IL-18 mRNA levels, Caspase-1 p20, NLRP3, ASC and GSDMD protein levels, and IL-1β and IL-18 contents, and increasing Bak-1, Bax, Cyt C and Caspase-3 mRNA levels and cleaved Caspase-3/Caspase-3 protein level, and downregulating Bcl-2 mRNA level and the ratio of Bcl-2 to Bax, respectively. Overall, the results illustrate that pyroptosis and apoptosis induced by Cd or/and Mo may be associated with activating the PTEN/PI3K/AKT pathway in the livers of ducks. There may be a synergy between these two elements.
镉(Cd)和过量钼(Mo)对动物有不良影响。然而,Cd 和 Mo 共同诱导鸭肝脏毒性的机制尚未完全阐明。为了探讨 Cd 和 Mo 共同暴露对鸭肝脏中 PTEN/PI3K/AKT 通路诱导的细胞焦亡和细胞凋亡的影响,将 40 只 7 日龄健康绍兴鸭()随机分为 4 组,在基础日粮中添加每千克(kg):对照组(0mg Mo 和 0mg Cd)、Mo 组(100mg Mo)、Cd 组(4mg Cd)和 Mo+Cd 组(100mg Mo 和 4mg Cd),进行 16 周的饲养管理。结果表明,Cd 或/和 Mo 导致鸭肝脏微量元素失衡、肝功能和组织形态学异常,并通过增加 PTENmRNA 和蛋白水平、降低 PI3K、AKTmRNA 和 p-AKT/AKT 蛋白水平激活 PTEN/PI3K/AKT 通路,从而引发细胞焦亡和细胞凋亡,上调 Caspase-1、NLRP3、NEK7、ASC、GSDME、GSDMA、IL-1β和 IL-18mRNA 水平,下调 Caspase-1 p20、NLRP3、ASC 和 GSDMD 蛋白水平,上调 IL-1β和 IL-18 含量,上调 Bak-1、Bax、Cyt C 和 Caspase-3mRNA 水平和裂解 Caspase-3/Caspase-3 蛋白水平,下调 Bcl-2mRNA 水平和 Bcl-2/Bax 比值。综上所述,Cd 或/和 Mo 诱导的细胞焦亡和细胞凋亡可能与鸭肝脏中 PTEN/PI3K/AKT 通路的激活有关,这两种元素之间可能存在协同作用。