近日，我院毒理学系研究团队在HFPO-DA (六氟环氧丙烷二聚体)暴露诱导鸡胚发育毒性方面取得新成果，为HFPO-DA的毒理学信息作出进一步补充，为HFPO-DA暴露的人群健康风险评估提供科学依据。相关研究成果以“Hexafluoropropylene oxide dimer acid (HFPO-DA) induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens: roles of peroxisome proliferator activated receptor alpha”为题，发表在期刊Environmental Pollution (IF=8.071)上(DOI 10.1016/j.envpol.2021.118112)。
传统PFASs (全氟及多氟烷基化合物)是一类常见持久性有机污染物，严重危害环境和生物健康，其使用受到严格限制。PFOA (全氟辛酸)是一种常用PFAS，而HFPO-DA是其常用替代物。HFPO-DA疏水疏油、表面张力小，常作为优良的表面活性剂，广泛应用于润滑剂、颜料、食品包装袋、车用橡胶皮垫、电镀、氟聚树脂等。但HFPO-DA的安全性仍不十分清楚，其毒理学信息依然存在大片空白。
由于HFPO-DA化学结构与PFOA类似，可能存在相似的毒理学效应，团队之前的研究已证实了PPARα在PFOA诱导的鸡胚心脏发育毒性中起重要作用，此次本课题组采用气室注射的方式对鸡胚进行HFPO-DA的暴露处理，探究其是否具有类似PFOA的发育毒性。在确定其诱导的发育毒性作用后，通过胚胎微注射手段对鸡胚进行PPARα沉默慢病毒转染，探究PPARα在HFPO-DA暴露诱导鸡胚发育毒性中扮演的角色。
研究发现，HFPO-DA (≥4 mg/kg蛋重)暴露能诱导鸡胚发育心脏毒性，包括心率升高和右心室壁变薄，这与PFOA暴露鸡胚观察到的毒性效应一致；以及诱导鸡胚发育肝脏毒性，以肝脂肪样变为主要表现。而PPARα沉默后使得心率升高，右心室壁变薄及肝脂肪样变的现象得以缓解，表明PPARα参与了HFPO-DA诱导的鸡胚发育性心脏和肝脏毒性。此外，在HFPO-DA暴露处理的鸡胚心脏组织中，PPARα下游基因CD36和EHHADH表达增强，PPARα沉默后其表达回降至正常水平；然而，在肝脏组织中只观察到CD36的表达增强，这可能提示HFPO-DA暴露诱导鸡胚心脏和肝脏毒性的毒性机制有所不同。这填补了HFPO-DA部分毒理学信息，为进一步深入探究其毒性机制提供了有力支持。
必赢线路检测中心卫生毒理系姜启晓老师为本文通讯作者，硕士研究生徐晓慧为本文第一作者。上述研究得到山东省自然科学基金(ZR2020MH335)和国家自然科学基金(81502835)的支持。
Recently, the research team of toxicology at School of Public Health, Qingdao University has made new progress in the study of HFPO-DA (hexafluoropropylene oxide dimer acid)-induced developmental toxicity in chicken embryos, which revealed new toxicological information of HFPO-DA and provides scientific evidence for the health risk assessment of HFPO-DA exposed population. The related research results were published in the Environmental Pollution (IF=8.017) (DOI1010.1016/j.envpol.2021.118112) under the title of “Hexafluoropropylene oxide dimer acid (HFPO-DA) induced developmental cardiotoxicity and hepatotoxicity in hatchling chickens: roles of peroxisome proliferator activated receptor alpha”.
Traditional PFASs (perfluorinated and polyfluoroalkyl compounds) are common persistent organic pollutants that pose significant environmental and biological health hazards and their uses are being phased out. PFOA (perfluorooctanoic acid) is a common PFAS, and HFPO-DA is a popular alternative compound of PFOA. HFPO-DA is an excellent surfactant with low surface tension and hydrophobic properties. It is widely used in lubricants, pigments, food packaging bags, automotive rubber pads, electroplating, fluorinated resins, etc. But the safety parameters of HFPO-DA remain unclear, and toxicological information largely remains to be elucidated.
HFPO-DA is chemically similar to PFOA and may have similar toxicological effects. Our previous studies confirmed that PPARα plays an important role in PFOA-induced developmental cardiotoxicity in chicken embryos. Therefore, in the current study, our group exposed chicken embryos to HFPO-DA by air cell injection to explore whether HFPO-DA has developmental toxicities similar to PFOA. After confirming the existence of developmental toxicities, chicken embryos were transfected with PPARα silencing lentivirus via embryo microinjection to investigate the role of PPARα in the developmental toxicities of chicken embryo induced by HFPO-DA exposure.
It was revealed that HFPO-DA (≥4 mg/kg egg weight) induced developmental cardiotoxicity in chicken embryos, including increased heart rate and thinning of right ventricular wall, which is consistent with the observed toxicological effects of PFOA exposure; HFPO-DA exposure also resulted in developmental hepatotoxicity in chicken embryo, mainly manifested in the form of steatosis.
The silencing of PPARα alleviated increase of heart rate, thinning of right ventricular wall and hepatic steatosis, suggesting that PPARα is involved in HFPO-DA induced developmental cardiotoxicity and hepatotoxicity in chicken embryos. In addition, enhanced expression of PPARα downstream genes, cluster of differentiation 36 (CD36) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), were observed in HFPO-DA exposed animal heart tissues, which can be abolished by PPARα silencing. However, only CD36 expression was effectively enhanced in exposed liver tissues, suggesting differential mechanism of toxicity in heart and liver tissues. These results fill in part of the toxicological information of HFPO-DA and provide strong support for further investigation for its mechanism of toxicity.
Associate professor Qixiao Jiang is the corresponding author of this study, and graduate student Xiaohui Xu is the first author. The above research was supported by the Natural Science Foundation of Shandong Province (ZR2020MH335) and the National Natural Science Foundation of China (81502835).
