Chen Qianqian, Cao Yu, Li Huiqi, Liu Huanpeng, Liu Yinai, Bi Liuliu, Zhao Haiyang, Jin Libo, Peng Renyi
Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, China.
Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang Province, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, China.
J Environ Manage. 2023 Nov 1;345:118702. doi: 10.1016/j.jenvman.2023.118702. Epub 2023 Aug 1.
The health damage caused by nanoplastics (NPs) pollution has become one of the global scientific problems to be solved urgently. However, the toxicological mechanism of NPs is complex, and the research progress of anti-toxicity is limited. Thus, it has potential application value to explore or develop drugs that can effectively alleviate or remove NPs with biological toxicity. In this research, 8 μM sodium nitroprusside (SNP) solution was used to treat zebrafish larvae with 20 mg/L NPs for up to 12 days, and the results showed that SNP treatments were effective in alleviating NPs-caused developmental toxicity in zebrafish larvae. Further examination of its signaling pathway revealed that NPs-induced oxidative stress was mitigated by activating the NO-sGC-cGMP signaling pathway and reduced most of the reactive oxygen species (ROS). Subsequently, we detected the key substances and the key enzymes involved in apoptosis and ferroptosis, and found that oxidative stress-induced mitochondria-dependent apoptosis and lipid peroxidation-caused ferroptosis were alleviated. Finally, observed the accumulation of NPs and ROS in the liver of zebrafish larvae, which is the target organ of immunotoxicity, and we found that SNP could alleviate NPs-caused inflammation by analyzing the fluorescence intensity of neutrophils and macrophages in transgenic zebrafish and detecting the expression of key immune genes. In conclusion, this research has shown for the first time that SNP treatment can significantly inhibit NPs-induced developmental toxicity, resulting from oxidative stress-induced apoptosis, ferroptosis and inflammation in zebrafish larvae.
纳米塑料（NPs）污染造成的健康损害已成为全球亟待解决的科学问题之一。然而，NPs的毒理学机制复杂，抗毒性研究进展有限。因此，探索或开发能有效减轻或消除具有生物毒性的NPs的药物具有潜在应用价值。在本研究中，用8μM硝普钠（SNP）溶液处理暴露于20mg/L NPs中的斑马鱼幼体长达12天，结果表明SNP处理可有效减轻NPs对斑马鱼幼体造成的发育毒性。对其信号通路的进一步研究表明，通过激活NO-sGC-cGMP信号通路减轻了NPs诱导的氧化应激，并减少了大部分活性氧（ROS）。随后，我们检测了凋亡和铁死亡过程中涉及的关键物质和关键酶，发现氧化应激诱导的线粒体依赖性凋亡和脂质过氧化引起的铁死亡得到缓解。最后，观察了NPs和ROS在斑马鱼幼体肝脏（免疫毒性的靶器官）中的积累情况，通过分析转基因斑马鱼中中性粒细胞和巨噬细胞的荧光强度以及检测关键免疫基因的表达，发现SNP可以减轻NPs引起的炎症。总之，本研究首次表明SNP处理可显著抑制NPs诱导的发育毒性，该毒性是由斑马鱼幼体氧化应激诱导的凋亡、铁死亡和炎症所致。
