Laboratory of Environmental Mutagenicity, Department of Biophysics and Biometry, Rio de Janeiro State University, Rio de Janeiro, Brazil.
Faculty of Pharmacy, Fluminense Federal University, Niteroi, Brazil.
J Toxicol Environ Health A. 2024 Mar 18;87(6):245-265. doi: 10.1080/15287394.2023.2294925. Epub 2024 Jan 10.
The consumption of dietary supplements to enhance physical performance has increased significantly in the last century, especially thermogenic pre-workout supplements. Nevertheless, this industry has faced criticism for inadequate safety measures surveillance in regulatory issues regarding their products. The aims of our study were to investigate two pre-workout supplements with respect to (1) mutagenicity utilizing /microsome assay; (2) genotoxicity employing cytokinesis-block micronucleus (CBMN) assay protocols; and (3) hepatocytoxicity using WST cell proliferation, activities of lactate dehydrogenase (LDH) and alkaline phosphatase using human liver carcinoma (HepG2) and mouse fibroblast (F C3H) cells. Oxidative stress was determined through glutathione (GSH) measurement and for predictions of pharmacokinetics and toxicity for the most abundant isolated substances present in these supplements. Both supplements induced mutagenicity in all examined bacterial strains, especially in the presence of exogenous metabolism. Further, tested supplements significantly elevated the formation of micronuclei (MN) as well as other cellular phenomena. Concentration- and time-dependent curves were observed for hepatotoxicity in both studied cell lines. In addition, both supplements decreased levels of intracellular and extracellular GSH. predictions showed that the isolated individual compounds failed to induce the observed outcomes. Our findings provide contributions to the molecular mechanisms underlying two pre-workout supplement-induced toxicity and the need for surveillance.
在上个世纪，人们大量消费膳食补充剂来提高身体性能，特别是发热的锻炼前补充剂。然而，由于监管问题，该行业在其产品的安全性措施监测方面面临着批评。我们的研究目的是调查两种锻炼前补充剂，具体如下：（1）利用微粒体试验检测其诱变活性；（2）采用细胞有丝分裂阻断微核（CBMN）试验方案检测其遗传毒性；（3）利用 WST 细胞增殖、人肝癌（HepG2）和小鼠成纤维细胞（F C3H）细胞中的乳酸脱氢酶（LDH）和碱性磷酸酶活性检测其肝细胞毒性。通过谷胱甘肽（GSH）测量来确定氧化应激情况，并对这些补充剂中最丰富的分离物质进行药代动力学和毒性预测。两种补充剂都在所有被检测的细菌菌株中诱导了突变，尤其是在外源性代谢存在的情况下。此外，测试的补充剂显著增加了微核（MN）的形成以及其他细胞现象。在两种研究的细胞系中，都观察到了细胞毒性的浓度和时间依赖性曲线。此外，两种补充剂都降低了细胞内和细胞外 GSH 的水平。预测表明，分离的单个化合物未能引起观察到的结果。我们的研究结果为两种锻炼前补充剂诱导毒性的分子机制提供了贡献，并需要进行监测。
