Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China.
Tieling City Inspection and Testing and Certification Service Center (Animal Product Safety Testing Station), Tieling 112000, China.
Oxid Med Cell Longev. 2020 Feb 18;2020:4048706. doi: 10.1155/2020/4048706. eCollection 2020.
The purpose of this study was to investigate the protective effect and mechanism of yeast selenium (Se-Y) on ochratoxin- (OTA-) induced nephrotoxicity of chickens. A total of 80 one-day-old healthy chickens were randomly divided into 4 equal groups: control, OTA (50 g/kg OTA), Se-Y (0.4 mg/kg Se-Y), and OTA+Se-Y (50 g/kg OTA+0.4 mg/kg Se-Y). In the OTA chickens, differences in body weight, kidney coefficient, biochemical histological analysis, antioxidant capability, and the expression levels of the PI3K/AKT and Nrf2/Keap1 signaling pathway-related genes were observed. The levels of total superoxide dismutase (T-SOD), antioxidant capacity (T-AOC), catalase (CAT), and glutathione (T-GSH) significantly decreased, but the malondialdehyde (MDA) level of the kidneys significantly increased in the OTA treatment group. More importantly, treatment with Se-Y improved the antioxidant enzyme activities within the kidneys of chickens exposed to OTA. In addition, administration of OTA resulted in apoptosis and was associated with decreased expression of AKT, PI3K, and Bcl-2, which in turn enhanced expression of Caspase3, Bax, and P53. However, Se-Y improved the antioxidant defense system through activation of the Nrf2/Keap1 signaling pathway. Gene expression of Nrf2 and its target genes (HO-1, GSH-px, GLRX2, MnSOD, and CAT) was downregulated following OTA exposure. Conversely, Se-Y treatment resulted in a significant upregulation of the same genes. Besides, significant downregulations of protein expression of HO-1, CAT, MnSOD, Nrf2, and Bcl-2 and a significant upregulation of Caspase3 and Bax levels were observed after contaminated with OTA. Notably, OTA-induced apoptosis and oxidative damage in the kidney of chickens were reverted back to normal level in the OTA+Se-Y group. Taken together, the data suggest that Se-Y alleviates OTA-induced nephrotoxicity in chickens, possibly through the activation of the PI3K/AKT and Nrf2/Keap1 signaling pathways.
本研究旨在探讨酵母硒（Se-Y）对赭曲霉毒素（OTA）诱导的鸡肾毒性的保护作用及其机制。将 80 只 1 日龄健康雏鸡随机分为 4 组：对照组、OTA（50μg/kg OTA）组、Se-Y（0.4mg/kg Se-Y）组和 OTA+Se-Y（50μg/kg OTA+0.4mg/kg Se-Y）组。观察 OTA 对鸡体重、肾脏系数、生化组织学分析、抗氧化能力以及 PI3K/AKT 和 Nrf2/Keap1 信号通路相关基因表达的影响。结果发现，OTA 组鸡总超氧化物歧化酶（T-SOD）、抗氧化能力（T-AOC）、过氧化氢酶（CAT）和谷胱甘肽（T-GSH）水平显著降低，而肾脏丙二醛（MDA）水平显著升高。更重要的是，Se-Y 改善了暴露于 OTA 的鸡肾脏中的抗氧化酶活性。此外，OTA 给药导致细胞凋亡，并与 AKT、PI3K 和 Bcl-2 表达降低有关，进而增强了 Caspase3、Bax 和 P53 的表达。然而，Se-Y 通过激活 Nrf2/Keap1 信号通路改善了抗氧化防御系统。Nrf2 及其靶基因（HO-1、GSH-px、GLRX2、MnSOD 和 CAT）的基因表达在 OTA 暴露后下调。相反，Se-Y 处理导致相同基因的显著上调。此外，在用 OTA 处理后，HO-1、CAT、MnSOD、Nrf2 和 Bcl-2 的蛋白表达显著下调，Caspase3 和 Bax 水平显著上调。值得注意的是，在 OTA+Se-Y 组中，OTA 诱导的鸡肾细胞凋亡和氧化损伤恢复到正常水平。综上所述，数据表明 Se-Y 可通过激活 PI3K/AKT 和 Nrf2/Keap1 信号通路减轻 OTA 诱导的鸡肾毒性。
