Department of Chemistry and Life Science, Suzhou University, Suzhou 234000, PR China; Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian, Liaoning, PR China; Dalian SEM Bioengineer and Biotech Ltd., Dalian, Liaoning, PR China.
Department of Chemistry and Life Science, Suzhou University, Suzhou 234000, PR China.
Environ Toxicol Pharmacol. 2012 Sep;34(2):484-494. doi: 10.1016/j.etap.2012.06.011. Epub 2012 Jul 1.
This study investigated the toxic effects of perfluorononanoic acid (PFNA), a persistent organic pollutant, on rat hepatocytes and Kupffer cells in vitro and in vivo. The results showed that administration of 5μM PFNA increased the viabilities of the hepatocytes and the Kupffer cells. An exposure of 50μM PFNA did not alter the viabilities of both cells, as well as the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the primary cultured hepatocytes or the hepatocytes co-cultured with Kupffer cells. An exposure of 100μM PFNA only decreased the viability of the hepatocytes. The administration of PFNA changed the hepatocyte expression of several genes related to lipid metabolism in vitro and in vivo. Oil Red O Staining revealed that 5mg PFNA/kg/D treatment lead to dramatic accumulation of lipids in rat liver. At the same dose PFNA damaged hepatocytes histopathologically. Up-regulated expressions of the inflammatory cytokines occurred in the Kupffer cells treated with 50μM PFNA and in the livers of the rat receiving a 5mg PFNA/kg/D treatment. In addition, these cytokines also increased in serum of the rat receiving higher dose of PFNA. In summary, on the one hand, PFNA exposure affected the viability of the hepatocytes, hepatic lipid metabolism and lead to lipid accumulation in liver. On the other hand, for the first time, PFNA exposure was demonstrated to affect the viability of the Kupffer cells as well as their expression of cytokines, which involved in regulation of various liver functions. Therefore, we conclude that both the hepatocyte and the Kupffer cell contribute to the observed hepatotoxicity of PFNA.
本研究探讨了全氟壬酸（PFNA）这一持久性有机污染物对大鼠肝细胞和枯否细胞的体外和体内的毒性作用。结果表明，5μM 的 PFNA 处理可提高肝细胞和枯否细胞的活力。50μM 的 PFNA 暴露并未改变两种细胞的活力，以及原代培养的肝细胞或与枯否细胞共培养的肝细胞中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的释放。只有 100μM 的 PFNA 暴露才降低了肝细胞的活力。PFNA 的处理改变了肝细胞中与脂代谢相关的几种基因的表达，无论是在体外还是在体内。油红 O 染色显示，5mg PFNA/kg/D 处理导致大鼠肝脏中脂质的大量积累。在相同剂量下，PFNA 对肝细胞造成组织病理学损伤。用 50μM PFNA 处理枯否细胞和给予大鼠 5mg PFNA/kg/D 处理均可导致促炎细胞因子在枯否细胞中的表达上调。此外，这些细胞因子在接受更高剂量 PFNA 处理的大鼠血清中也增加。总之，一方面，PFNA 暴露会影响肝细胞的活力、肝内脂质代谢，并导致肝脏内脂质堆积。另一方面，PFNA 暴露首次被证明会影响枯否细胞的活力及其细胞因子的表达，这涉及到对各种肝脏功能的调节。因此，我们得出结论，肝细胞和枯否细胞均参与了 PFNA 观察到的肝毒性。
