Di Giacomo Silvia, Di Sotto Antonella, Percaccio Ester, Scuotto Erica, Battistelli Cecilia, Mazzanti Gabriela, Menniti-Ippolito Francesca, Ippoliti Ilaria
Department of Food Safety, Nutrition and Veterinary Public Health, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Antioxidants (Basel). 2023 Sep 16;12(9):1771. doi: 10.3390/antiox12091771.
Overweight and obesity prevalence has increased worldwide. Apart from conventional approaches, people also resort to botanical supplements for reducing body weight, although several adverse events have been associated with these products. In this context, the present study aimed at evaluating the toxicity of -based products and shedding light on the mechanisms involved. The suspected hepatotoxic reactions related to -containing products collected within the Italian Phytovigilance System (IPS) were examined. Then, an in vitro study was performed to evaluate the possible mechanisms responsible for the liver toxicity, focusing on the modulation of oxidative stress and Nrf2 expression. From March 2002 to March 2022, the IPS collected eight reports of hepatic adverse reactions related to , which exclusively involved women and were mostly severe. The causality assessment was probable in three cases, while it was possible in five. In the in vitro experiments, a low cytotoxicity of was observed. However, its combination with montelukast greatly reduced cell viability, increased the intracellular ROS levels, and affected the cytoplasmic Nrf2 expression, thus suggesting an impairment of the antioxidant and cytoprotective defenses. Overall, our results support the safety concerns about -containing supplements and shed light on the possible mechanisms underpinning its hepatotoxicity.
超重和肥胖的患病率在全球范围内呈上升趋势。除了传统方法外，人们还求助于植物性补充剂来减轻体重，尽管这些产品已出现了一些不良事件。在此背景下，本研究旨在评估基于[具体物质]的产品的毒性，并阐明其中涉及的机制。对意大利植物警戒系统（IPS）收集的与含[具体物质]产品相关的疑似肝毒性反应进行了检查。然后，进行了一项体外研究，以评估可能导致肝脏毒性的机制，重点关注氧化应激的调节和Nrf2表达。从2002年3月到2022年3月，IPS收集了8份与[具体物质]相关的肝脏不良反应报告，这些报告均只涉及女性，且大多较为严重。因果关系评估在3例中为“很可能”，在5例中为“可能”。在体外实验中，观察到[具体物质]的细胞毒性较低。然而，它与孟鲁司特联合使用时，大大降低了细胞活力，增加了细胞内ROS水平，并影响了细胞质Nrf2表达，从而表明抗氧化和细胞保护防御功能受损。总体而言，我们的结果支持了对含[具体物质]补充剂安全性的担忧，并阐明了其肝毒性潜在的可能机制。
