Fluoride is considered as one of the most ubiquitous environmental pollutants. Numerous studies have linked reactive oxygen species (ROS)-dependent oxidative damage with fluoride intoxication, which could be prevented by antioxidants. However, the metabolomic changes induced by ROS disruptions in fluoride intoxication are yet unknown. The present study aimed to provide novel mechanistic insights into the fluoride-induced oxidative damage and to investigate the potential protective effects of ethanolic extract of Prunella vulgaris (natural antioxidant, PV) against fluoride-induced oxidative damage. The serum biochemical indicators related to fluoride-induced oxidative damage, such as lipid peroxidation parameter, inflammation and marker enzymes in the liver increased significantly in the fluoride-treated group, while antioxidant enzymes were decreased. However, PV treatment restored the level of these biochemical indicators, indicating satisfactory antioxidant, anti-inflammatory, and hepatoprotective potential of PV. The metabolomics analysis in the serum was performed by liquid chromatography–mass spectroscopy, whereas the fluoride treatment caused severe metabolic disorders in rats, which could be improved by PV. The differential metabolites screened by multivariate analysis after fluoride and PV treatment, were organic acids, fatty acids, and lipids. These differential metabolites represented disorders of glyoxylate and dicarboxylate metabolism and the citrate cycle (TCA) according to metabolic pathway analysis in fluoride treatment rats. Interestingly, the result of metabolic pathway analysis of post-treatment with PV was consistent with that of fluoride treatment, indicating that the energy metabolism plays a major role in the progress of fluoride-induced oxidative damage, as well as the therapeutic effect of PV. These findings provided a theoretical basis for understanding the mechanism underlying metabolic disorders of fluoride toxicity and the effect of PV.

中文翻译：

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夏枯草对氟化物氧化损伤的代谢组学治疗作用

氟化物被认为是最普遍的环境污染物之一。许多研究已将活性氧 (ROS) 依赖性氧化损伤与氟化物中毒联系起来，这可以通过抗氧化剂来预防。然而，氟中毒中ROS破坏引起的代谢组学变化尚不清楚。本研究旨在为氟化物诱导的氧化损伤提供新的机制见解，并研究夏枯草乙醇提取物的潜在保护作用（天然抗氧化剂，PV）对抗氟化物引起的氧化损伤。与氟化物引起的氧化损伤相关的血清生化指标，如脂质过氧化参数、炎症和肝脏中的标志酶在氟化物治疗组中显着增加，而抗氧化酶则降低。然而，PV 治疗恢复了这些生化指标的水平，表明 PV 具有令人满意的抗氧化、抗炎和保肝潜力。血清中的代谢组学分析是通过液相色谱-质谱法进行的，而氟化物处理会导致大鼠严重的代谢紊乱，PV 可以改善这种情况。在氟化物和 PV 处理后通过多变量分析筛选的差异代谢物是有机酸、脂肪酸和脂质。根据氟化物治疗大鼠的代谢途径分析，这些差异代谢物代表乙醛酸和二羧酸代谢紊乱以及柠檬酸循环 (TCA)。有趣的是，PV处理后的代谢途径分析结果与氟化物处理的结果一致，表明能量代谢在氟化物诱导的氧化损伤的进展以及PV的治疗效果中起主要作用。这些发现为理解氟化物毒性代谢紊乱的机制和PV的影响提供了理论基础。PV处理后代谢途径分析结果与氟化物处理结果一致，表明能量代谢在氟化物诱导的氧化损伤的进展以及PV的治疗效果中起主要作用。这些发现为理解氟化物毒性代谢紊乱的机制和PV的影响提供了理论基础。PV处理后代谢途径分析结果与氟化物处理结果一致，表明能量代谢在氟化物诱导的氧化损伤的进展以及PV的治疗效果中起主要作用。这些发现为理解氟化物毒性代谢紊乱的机制和PV的影响提供了理论基础。