Miyagi Prefectural Sendai Livestock Hygiene Service Center, Anyoji, Miyagino, Sendai, Miyagi, Japan.
Cellular Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Aramaki Aza Aoba, Aoba, Sendai, Miyagi, Japan.
PLoS One. 2019 Jan 4;14(1):e0210110. doi: 10.1371/journal.pone.0210110. eCollection 2019.
It is evident that some perfluoroalkyl acids (PFAAs), a group of globally dispersed pollutants, have long biological half-lives in humans and farm animals. However, the effects of PFAAs in domestic animals have not been fully elucidated. The present study investigated how exposure to a single dose of a mixture of 10 PFAAs influenced hepatic and renal gene expression and histopathology, as well as plasma clinical biochemistry, in microminipigs (MMPigs) over 21 days. In animals treated with PFAAs, the mRNA expression of twelve genes related to fatty acid metabolism was upregulated in the kidney, while only few of these genes were induced in the liver. The expression of several kidney injury-associated genes such as, IGFBP1, IGFBP6, GCLC X2, GCLC X3, MSGT1, OLR1 was upregulated in the kidney. Interestingly, the expression of IGFBP-genes was differentially altered in the liver and kidney. Our findings thus identified hepato-renal gene expression changes in MMPigs that were associated with various molecular pathways including peroxisome proliferation, lipid metabolism, kidney injury, and apoptosis. Furthermore, serum HDL levels were significantly decreased following exposure to PFAAs, whereas no significant histopathological changes were detected, as compared to the vehicle group. Taken together, the present study provided the first indication that a single exposure to a mixture of PFAAs can produce changes in MMPig renal gene expression that were observed three weeks post exposure, suggesting that more attention should be paid to the kidney as a primary target organ of PFAAs.
显然，全氟烷基酸（PFAAs）是一组在全球范围内分布的污染物，它们在人类和农场动物体内的生物半衰期很长。然而，PFAAs 对家畜的影响尚未完全阐明。本研究调查了单剂量混合 10 种 PFAAs 暴露对微型猪（MMPigs）肝肾功能基因表达和组织病理学以及血浆临床生物化学的影响，为期 21 天。在接受 PFAAs 处理的动物中，肾脏中与脂肪酸代谢相关的 12 个基因的 mRNA 表达上调，而肝脏中仅有少数这些基因被诱导。几种与肾损伤相关的基因，如 IGFBP1、IGFBP6、GCLC X2、GCLC X3、MSGT1、OLR1 在肾脏中表达上调。有趣的是，IGFBP-基因在肝脏和肾脏中的表达存在差异。因此，我们的研究结果确定了 MMPigs 肝肾功能基因表达的变化，这些变化与各种分子途径有关，包括过氧化物酶体增殖、脂质代谢、肾损伤和细胞凋亡。此外，与对照组相比，暴露于 PFAAs 后血清高密度脂蛋白（HDL）水平显著降低，而未检测到明显的组织病理学变化。总之，本研究首次表明，单次暴露于 PFAAs 混合物可导致 MMPig 肾脏基因表达发生变化，这些变化在暴露后 3 周即可观察到，这表明应更加关注肾脏作为 PFAAs 的主要靶器官。
