Campos Glaucia Maria, Santos Péterson Alves, Uczay Mariana, Pflüger Pricila, Mendes Thaís Lemos, Fontenla Jose Angel, Pereira Patrícia
Laboratory of Neuropharmacology and Preclinical Toxicology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
GI-1684 Laboratory of Central Nervous System Pharmacology (Faculty of Pharmacy), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain.
J Appl Toxicol. 2025 Feb;45(2):339-349. doi: 10.1002/jat.4705. Epub 2024 Oct 4.
Gamma-decanolactone (GD) is a monoterpene compound with anticonvulsant, antiparkinsonian, and neuroprotective effects in preclinical trials. This study aimed to evaluate the toxicity and antioxidant profile of GD in silico and in the Caenorhabditis elegans (C. elegans) experimental model. The C. elegans was used to determine the median lethal concentration (LC) of GD, as well as its effect on survival, development, reproduction, pharyngeal pumping, and stress resistance assays. The in silico study did not indicate hepatotoxic, cardiotoxic, or mutagenic potential to GD. It reduced the worms' survival, both at the L1 and L4 stages, in a concentration-dependent manner with an LC value of 212.16 ± 5.56 μmol/mL. GD did not alter the development, reproduction, and pharyngeal pumping under normal experimental conditions in the three concentrations tested (25, 50, and 100 μmol/mL). In the thermal stress assay, GD did not change the survival pattern of the worms. Hydrogen peroxide (HO) reduced the survival of C. elegans and decreased the number of pharyngeal pumping, with these effects being reversed by GD. Also, GD presents an antioxidant activity by modulation the expression of the stress response genes such as sod-3, ctl-1,2,3, and gst-4. In conclusion, GD showed low toxicity in the C. elegans model and antioxidant profile both in the in silico study and in vivo assays.
γ-癸内酯（GD）是一种单萜类化合物，在临床前试验中具有抗惊厥、抗帕金森病和神经保护作用。本研究旨在通过计算机模拟和秀丽隐杆线虫（C. elegans）实验模型评估GD的毒性和抗氧化特性。利用秀丽隐杆线虫确定GD的半数致死浓度（LC），以及其对生存、发育、繁殖、咽泵动和抗应激能力检测的影响。计算机模拟研究未表明GD具有肝毒性、心脏毒性或致突变性。它在L1和L4阶段均以浓度依赖性方式降低了线虫的存活率，LC值为212.16±5.56μmol/mL。在测试的三种浓度（25、50和100μmol/mL）下，正常实验条件下GD未改变发育、繁殖和咽泵动情况。在热应激试验中，GD未改变线虫的存活模式。过氧化氢（HO）降低了秀丽隐杆线虫的存活率并减少了咽泵动次数，而这些作用被GD逆转。此外，GD通过调节应激反应基因如sod-3、ctl-1、2、3和gst-4的表达呈现抗氧化活性。总之，在计算机模拟研究和体内试验中，GD在秀丽隐杆线虫模型中显示出低毒性和抗氧化特性。
