6PPD-quinone (6PPD-Q) is frequently detected in various environmental media, and the environmentally relevant concentrations can be fatal to Oncorhynchus mykiss. Notably, 6PPD-Q has two enantiomers (S-6PPD-Q and R-6PPD-Q). In this study, O. mykiss was separately exposed to each enantiomer and racemate of 6PPD-Q for 96 h at environmentally relevant concentrations, and livers were collected. Effects on the biochemical, pathological, and ultrastructural changes were assessed, and metabolomics was conducted to elucidate the potential hepatotoxicity mechanism. Compared with the control treatment, the levels of catalase (CAT, all treatments except for 0.1 μg/L rac-6PPD-Q), and glutathione-S-transferase (GST, all treatments) significantly declined. Hepatocyte space became smaller, nuclear morphology changed, and nucleolysis occurred. Mitochondrial malformation and vesicle-like structure dilation of the endoplasmic reticulum (ER) were observed in the hepatocytes, which was most serious after S-6PPD-Q exposure. Some amino acid metabolism, folate biosynthesis, taurine and hypotaurine metabolism and purine metabolism were disturbed, consistent with mitochondrial dysfunction and ER stress. The differential metabolites were in the order of S-6PPD-Q (216) > rac-6PPD-Q (88) > R-6PPD-Q (56). Thus, 6PPD-Q-induced hepatic mitochondrial dysfunction and ER stress, causing metabolic disturbance and oxidative stress might be the toxic mechanism of 6PPD-Q in O. mykiss liver, and S-6PPD-Q effects were the most serious.

中文翻译：

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在 Oncorhynchus mykiss 中，环境相关浓度的 S-6PPD-醌比 R-对映异构体和外消旋体引起更严重的肝毒性


6PPD-醌 （6PPD-Q） 经常在各种环境介质中检测到，与环境相关的浓度对 Oncorhynchus mykiss 可能是致命的。值得注意的是，6PPD-Q 有两种对映异构体 （S-6PPD-Q 和 R-6PPD-Q）。在本研究中，将 O. mykiss 分别暴露于环境相关浓度的 6PPD-Q 的每个对映异构体和外消旋体 96 小时，并收集肝脏。评估对生化、病理和超微结构变化的影响，并进行代谢组学以阐明潜在的肝毒性机制。与对照处理相比，过氧化氢酶 （CAT，除 0.1 μg/L rac-6PPD-Q 外的所有处理） 和谷胱甘肽-S-转移酶 （GST，所有处理） 水平显着下降。肝细胞间隙变小，核形态改变，发生核溶解。在肝细胞中观察到线粒体畸形和内质网 （ER） 的囊泡样结构扩张，其中 S-6PPD-Q 暴露后最为严重。一些氨基酸代谢、叶酸生物合成、牛磺酸和次牛磺酸代谢以及嘌呤代谢受到干扰，与线粒体功能障碍和 ER 应激一致。差异代谢物依次为 S-6PPD-Q （216） > rac-6PPD-Q （88） > R-6PPD-Q （56）。因此，6PPD-Q 诱导的肝脏线粒体功能障碍和 ER 应激，引起代谢紊乱和氧化应激可能是 6PPD-Q 在 O. mykiss 肝脏中的毒性机制，其中 S-6PPD-Q 效应最严重。