Rao Gan, Zhong Gaolong, Hu Ting, Wu Shaofeng, Tan Jiajia, Zhang Xiaoyong, Huang Riming, Tang Zhaoxin, Hu Lianmei
College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Joint Laboratory of Guangdong Province and Hong Kong Region On Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
Biol Trace Elem Res. 2023 Mar;201(3):1407-1417. doi: 10.1007/s12011-022-03219-1. Epub 2022 Apr 2.
Arsenic is a common environmental pollutant and poses a serious threat to human and animal health. In this study, we used the ducks to mimic arsenic trioxide (ATO) exposure and investigated the mechanism of cardiac toxicity. The results indicated that ATO inhibited the body and organ growth of ducks, led to an increase in LDH content, and caused obvious deformity, ischemia infarction. It is found that ATO exacerbated the swell of mitochondrial and the contraction of cell nuclei in the heart of ducks through transmission electron microscopy (TEM). ATO also induced an increase in MDA content; inhibited the activation of the Nrf 2 pathway; downregulated the expression of mRNA and protein of Nrf 2, HO-1, and SOD-1; and upregulated the expression of mRNA and protein of Keap 1. At the same time, ATO induced apoptosis which not only upregulated the expression levels of mRNA and proteins (Caspase 3, Cyt-C, P53, Bax) but also decreased the mRNA and protein expression level of Bcl-2. These results indicated that ATO can lead to oxidative stress and apoptosis in the heart of ducks. In general, our research shows that ATO triggers mitochondrial dysfunction, oxidative stress, and apoptosis via Nrf 2/Caspase 3 signaling pathway in the heart of ducks.
砷是一种常见的环境污染物，对人类和动物健康构成严重威胁。在本研究中，我们用鸭来模拟三氧化二砷（ATO）暴露，并研究心脏毒性的机制。结果表明，ATO抑制鸭的身体和器官生长，导致乳酸脱氢酶（LDH）含量增加，并引起明显畸形、缺血梗死。通过透射电子显微镜（TEM）发现，ATO加剧了鸭心脏线粒体肿胀和细胞核收缩。ATO还诱导丙二醛（MDA）含量增加；抑制核因子E2相关因子2（Nrf 2）通路的激活；下调Nrf 2、血红素加氧酶-1（HO-1）和超氧化物歧化酶-1（SOD-1）的mRNA和蛋白表达；上调 Kelch样环氧氯丙烷相关蛋白1（Keap 1）的mRNA和蛋白表达。同时，ATO诱导细胞凋亡，不仅上调了mRNA和蛋白（半胱天冬酶3（Caspase 3）、细胞色素C（Cyt-C）、P53、Bax）的表达水平，还降低了B细胞淋巴瘤因子2（Bcl-2）的mRNA和蛋白表达水平。这些结果表明，ATO可导致鸭心脏氧化应激和细胞凋亡。总体而言，我们的研究表明，ATO通过鸭心脏中的Nrf 2/Caspase 3信号通路引发线粒体功能障碍、氧化应激和细胞凋亡。
