Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Department of Physiology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Int J Mol Sci. 2023 Sep 15;24(18):14129. doi: 10.3390/ijms241814129.
The liver is the organ responsible for the metabolism and detoxification of BPF, the BPA analogue that is replacing it in plastic-based products. It is not known whether BPF can trigger inflammatory responses via the NLRP3 inflammasome, which plays a major role in the development of liver disease. The aim of this study was to evaluate nitrosative stress species (RNS) and NLRP3 inflammasome activation in the liver of lactating dams after BPF exposure. Moreover, it was studied whether this effect could also be observed in the liver of female and male offspring at postnatal day 6 (PND6). 36 Long Evans rats were randomly distributed according to oral treatment into three groups: Control, BPF-low dose (LBPF; 0.0365 mg/kg b.w./day) group and BPF-high dose (HBPF; 3.65 mg/kg b.w./day) group. The levels of nitrosative stress-inducing proteins (eNOS, iNOS, HO-1d), NLRP3 inflammasome components (NLRP3, PyCARD, CASP1) and proinflammatory cytokines (IL-1β, IL-18, IFN-γ and TNF-α) were measured by gene and protein expression in the liver of lactating dams and in female and male PND6 offspring. Lactating dams treated with LBPF showed a significant increase in iNOS and HO-1d, activation of NLRP3 components (NLRP3, PyCARD, CASP1) and promoted the release of proinflammatory cytokines such as IL-1β, IL-18, IFN-γ and TNF-α. Similar effects were found in female and male PND6 offspring after perinatal exposure. LBPF oral administration and perinatal exposure caused an increase of nitrosative stress markers and proinflammatory cytokines. Also, NLRP3 inflammasome activation was significantly increased in in the liver of lactating dams and PND6 offspring.
肝脏是负责 BPF（双酚 F，一种替代塑料产品中 BPA 的类似物）代谢和解毒的器官。目前尚不清楚 BPF 是否可以通过 NLRP3 炎性小体引发炎症反应，NLRP3 炎性小体在肝脏疾病的发展中起着重要作用。本研究旨在评估 BPF 暴露后哺乳期母鼠肝脏中的硝化应激物质（RNS）和 NLRP3 炎性小体的激活情况。此外，还研究了这种影响是否也可以在产后第 6 天（PND6）的雌性和雄性后代的肝脏中观察到。36 只长爪沙鼠被随机分为三组，根据口服处理方式分为：对照组、BPF 低剂量（LBPF；0.0365mg/kg bw/天）组和 BPF 高剂量（HBPF；3.65mg/kg bw/天）组。通过基因和蛋白表达，测量了哺乳期母鼠和雌性及雄性 PND6 后代肝脏中诱导硝化应激的蛋白（eNOS、iNOS、HO-1d）、NLRP3 炎性小体成分（NLRP3、PyCARD、CASP1）和促炎细胞因子（IL-1β、IL-18、IFN-γ和 TNF-α）的水平。用 LBPF 处理的哺乳期母鼠显示 iNOS 和 HO-1d 显著增加，NLRP3 成分（NLRP3、PyCARD、CASP1）被激活，并促进促炎细胞因子如 IL-1β、IL-18、IFN-γ和 TNF-α的释放。围产期暴露后，雌性和雄性 PND6 后代也出现了类似的影响。LBPF 口服给药和围产期暴露导致硝化应激标志物和促炎细胞因子增加。此外，哺乳期母鼠和 PND6 后代肝脏中的 NLRP3 炎性小体激活也明显增加。
