School of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, PR China; College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
Sci Total Environ. 2024 Aug 25;940:173575. doi: 10.1016/j.scitotenv.2024.173575. Epub 2024 May 31.
Decabromodiphenyl ethane (DBDPE) and polystyrene nanoplastics (PS-NPs) are emerging pollutants that seriously threaten the ecological safety of the aquatic environment. However, the hepatotoxicity effect of their combined exposure on aquatic organisms has not been reported to date. In, this study, the effects of single or co-exposure of DBDPE and PS-NPs on grass carp hepatocytes were explored and biomarkers related to oxidative stress, ferroptosis, and inflammatory cytokines were evaluated. The results show that both single and co-exposure to DBDPE and PS-NPs caused oxidative stress. Oxidative stress was induced by increasing the contents of pro-oxidation factors (ROS, MDA, and LPO), inhibiting the activity of antioxidant enzymes (CAT, GPX, T-SOD, GSH, and T-AOC), and downregulating the mRNA expressions of antioxidant genes (GPX1, GSTO1, SOD1, and CAT); the effects of combined exposure were stronger overall. Both single and co-exposure to DBDPE and PS-NPs also elevated Fe content, promoted the expressions of TFR1, STEAP3, and NCOA4, and inhibited the expressions of FTH1, SLC7A11, GCLC, GSS, and GPX4; these effects resulted in iron overload-induced ferroptosis, where co-exposure had stronger adverse effects on ferroptosis-related biomarkers than single exposure. Moreover, single or co-exposure enhanced inflammatory cytokine levels, as evidenced by increased mRNA expressions of IL-6, IL-12, IL-17, IL-18, IL-1β, TNF-α, IFN-γ, and MPO. Co-exposure exhibited higher expression of pro-inflammatory cytokines compared to single exposure. Interestingly, the ferroptosis inhibitor ferrostatin-1 intervention diminished the above changes. In brief, the results suggest that DBDPE and PS-NPs trigger elevated levels of inflammatory cytokines in grass crap hepatocytes. This elevation is achieved via oxidative stress and iron overload-mediated ferroptosis, where cytotoxicity was stronger under co-exposure compared to single exposure. Overall, the findings contribute to elucidating the potential hepatotoxicity mechanisms in aquatic organisms caused by co-exposure to DBDPE and PS-NPs.
十溴二苯乙烷（DBDPE）和聚苯乙烯纳米塑料（PS-NPs）是新兴的污染物，它们严重威胁着水生环境的生态安全。然而，迄今为止，尚未有报道表明它们的联合暴露对水生生物具有肝毒性作用。在本研究中，我们探讨了 DBDPE 和 PS-NPs 单一或联合暴露对草鱼肝细胞的影响，并评估了与氧化应激、铁死亡和炎症细胞因子相关的生物标志物。结果表明，DBDPE 和 PS-NPs 的单一或联合暴露均会导致氧化应激。氧化应激是通过增加促氧化因子（ROS、MDA 和 LPO）的含量、抑制抗氧化酶（CAT、GPX、T-SOD、GSH 和 T-AOC）的活性以及下调抗氧化基因（GPX1、GSTO1、SOD1 和 CAT）的 mRNA 表达来诱导的；联合暴露的作用总体上更强。DBDPE 和 PS-NPs 的单一或联合暴露还会升高铁含量，促进 TFR1、STEAP3 和 NCOA4 的表达，并抑制 FTH1、SLC7A11、GCLC、GSS 和 GPX4 的表达；这些作用导致铁过载诱导的铁死亡，联合暴露对铁死亡相关生物标志物的不良影响强于单一暴露。此外，单一或联合暴露会增强炎症细胞因子水平，这表现为 IL-6、IL-12、IL-17、IL-18、IL-1β、TNF-α、IFN-γ和 MPO 的 mRNA 表达增加。与单一暴露相比，联合暴露表现出更高的促炎细胞因子表达。有趣的是，铁死亡抑制剂 ferrostatin-1 干预减弱了上述变化。总之，这些结果表明 DBDPE 和 PS-NPs 会引发草鱼肝细胞中炎症细胞因子水平的升高。这种升高是通过氧化应激和铁过载介导的铁死亡实现的，与单一暴露相比，联合暴露的细胞毒性更强。总的来说，这些发现有助于阐明 DBDPE 和 PS-NPs 联合暴露对水生生物潜在的肝毒性机制。
