Liu Zheng, Wang Hui, Zhang Wenxiu, Yuan Ziao, Yuan Hongyi, Liu Xueting, Zhang Minghai, Guo Xuesong, Guan Weijun
a College of Food Science and Engineering , Jinzhou Medical University , Jinzhou , Liaoning , China.
b Institute of Animal Science , Chinese Academy of Agricultural Sciences , Beijing , China.
Drug Chem Toxicol. 2018 Apr;41(2):188-198. doi: 10.1080/01480545.2017.1337125. Epub 2017 Jun 21.
Lead (Pb) is a poisonous heavy metal that causes many pathophysiological effects in living systems. Its toxicological effects are well known as it causes apoptosis of several cell types and tissues. This study aimed to determine the criteria required for early diagnosis of Pb poisoning in the Siberian tiger using a tiger population in China, to identify a safety Pb concentration threshold, and to provide suggestions for preventing Pb poisoning in Siberian tigers. We investigated the apoptotic effects of Pb (0, 32, 64, and 125 μM) for 12-48 h on Siberian tiger fibroblasts in vitro. Typical apoptotic effects were observed after Pb exposure. Pb strongly blocked DNA synthesis in the G0/G1 phase and induced cell apoptosis in a dose- and time-dependent manner. Intracellular free calcium (Ca) levels, reactive oxygen species levels, and efflux of extracellular Ca were increased. The mitochondrial membrane potential was lowered. Caspase-3, -8, and -9 activities were increased when fibroblasts were treated with 32, 64, and 125 μM Pb. The gene expression levels of Bax, caspase-3, -8, Fas, and p53 were increased, while that of Bcl-2 was decreased. Calcium homeostasis and mitochondrial function were disturbed. Ca efflux, oxidative damage, activation of caspases, and regulation of Bax, Bcl-2, caspase-3, -8, Fas, and p53 gene expression played an important role in the apoptotic effects. The disorder of intracellular homeostasis was the trigger for apoptosis in Siberian tiger fibroblasts.
铅（Pb）是一种有毒重金属，会对生物系统产生多种病理生理影响。其毒理学效应广为人知，因为它会导致多种细胞类型和组织发生凋亡。本研究旨在利用中国的老虎种群确定西伯利亚虎铅中毒早期诊断所需的标准，确定安全的铅浓度阈值，并为预防西伯利亚虎铅中毒提供建议。我们在体外研究了铅（0、32、64和125 μM）对西伯利亚虎成纤维细胞12 - 48小时的凋亡作用。铅暴露后观察到典型的凋亡效应。铅强烈阻断G0/G1期的DNA合成，并以剂量和时间依赖性方式诱导细胞凋亡。细胞内游离钙（Ca）水平、活性氧水平以及细胞外钙外流增加。线粒体膜电位降低。当用32、64和125 μM铅处理成纤维细胞时，半胱天冬酶-3、-8和-9的活性增加。Bax、半胱天冬酶-3、-8、Fas和p53的基因表达水平升高，而Bcl-2的基因表达水平降低。钙稳态和线粒体功能受到干扰。钙外流、氧化损伤、半胱天冬酶的激活以及Bax、Bcl-2、半胱天冬酶-3、-8、Fas和p53基因表达的调节在凋亡效应中起重要作用。细胞内稳态紊乱是西伯利亚虎成纤维细胞凋亡的触发因素。
