The increasing gas emissions and industrial wastewater discharge of anthropogenic hexavalent chromium (Cr(VI)) have been growing health concerns to the high trophic level marine mammals. Our previous studies showed that Indo-Pacific humpback dolphin (Sousa chinensis), stranded on the Pearl River Estuary region, contained exceedingly high levels of Cr in their skin-tissues. Unfortunately, the molecular toxic mechanisms on this mammal are absent, limiting our understanding of the eco-physiological impacts of Cr(VI) on dolphins. Thus, the cytotoxicity effects of Cr(VI) were analyzed on fibroblasts we isolated from the skin of S. chinensis (ScSF). This study showed that Cr(VI) markedly inhibited the viability of ScSF cells via induction of apoptosis accompanied by an increase in the production of reactive oxygen species and the population of G2/M arrest or apoptotic sub-G1 phase cells, up-regulation of p53, and activation of caspase-3. Further investigation on intracellular mechanisms indicated that Cr(VI) induced depletion of mitochondrial membrane potential in cells through regulating the expression of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) proteins, resulting in decrease of the ATP level, cytochrome c release from mitochondria into cytosol, and the activation of caspase-9. Furthermore, antioxidants N-acetylcysteine and vitamin C displayed chemoprotective activity against Cr(VI) via suppression of p53 expression, indicating that the Cr(VI)-induced cell death may be mediated by oxidative stress. Overall, these results provide insights into the potential mechanisms underlying the cytotoxicity of Cr(VI) in Indo-Pacific humpback dolphin skin cells, offer experimental support for the proposed protective role of antioxidants in Cr(VI)-induced toxicity, and suggest that Cr(VI) contamination is one of key health concern issues for the protection of Indo-Pacific humpback dolphin.

人为污染的六价铬（Cr（VI））的气体排放量和工业废水排放量不断增加，对营养水平较高的海洋哺乳动物造成了越来越多的健康问题。我们以前的研究表明，滞留在珠江口地区的印度太平洋驼背海豚（Sousa chinensis）的皮肤组织中铬含量极高。不幸的是，这种哺乳动物缺乏分子毒性机制，这限制了我们对六价铬对海豚的生态生理影响的理解。因此，分析了Cr（VI）对我们从中华链球菌皮肤中分离出的成纤维细胞的细胞毒性作用。（ScSF）。这项研究表明Cr（VI）通过诱导凋亡显着抑制ScSF细胞的活力，伴随着活性氧的产生以及G2 / M阻滞或凋亡的亚G1期细胞数量的增加，以及上皮细胞的上调。p53和caspase-3的激活。对细胞内机制的进一步研究表明，Cr（VI）通过调节抗凋亡（Bcl-2）和促凋亡（Bax）蛋白的表达诱导细胞线粒体膜电位的消耗，从而导致ATP水平，细胞色素的降低c从线粒体释放到细胞质中，并激活caspase-9。此外，抗氧化剂N-乙酰半胱氨酸和维生素C通过抑制p53表现出对Cr（VI）的化学保护活性表达，表明Cr（VI）诱导的细胞死亡可能是由氧化应激介导的。总体而言，这些结果提供了对印度-太平洋驼背海豚皮肤细胞中Cr（VI）潜在细胞毒性的潜在机制的见解，为拟议的抗氧化剂在Cr（VI）诱导的毒性中的保护作用提供了实验支持，并表明Cr （VI）污染是保护印度太平洋驼背海豚的关键健康问题之一。