Gamma‐Decanolactone Increases Stress Resistance and Improves Toxicity Parameters on the <scp><i>Caenorhabditis elegans</i></scp> Alternative Model

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 (LC₅₀) 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 LC₅₀ 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 (H₂O₂) 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.