Toxicogenetic profile and antioxidant evaluation of gamma-terpinene: Molecular docking and <i>in vitro</i> and <i>in vivo</i> assays

Gamma-terpinene (γ-TPN) is found in several plant species, such as thyme, eucalyptus, rosemary, black cumin, oregano, among others, and is known for antimicrobial, antiparasitic, antinociceptive, anticancer, antiplatelet, and insecticidal activities. Based on this, it was assessed its toxicogenetic and antioxidant profile using <i>in silico</i>, <i>in vitro</i> and <i>in vivo</i> replacement assays. The compound was moderately toxic on <i>Artemia salina</i> nauplii [LC₅₀ value of 136.1 (81.8 - 158.7) µM] and reduced proliferation of melanoma B16-F10 [IC₅₀ value of 38.19 (26.82 - 54.52) μM] tumor cells, without affecting viability of normal RAW 264.7 macrophages and mammalian erythrocytes' membrane. γ-TPN (12.5, 25 and 50 µM) intensively reduced the mitotic index (MI) of dividing <i>Allium cepa</i> meristematic cells in a non-concentration-dependent way and caused increasing in interphase and reduction in prophase cells (p < 0.05). The monoterpene showed <i>in silico</i> affinity to the enzymes catalase and glutathione reductase and <i>in vivo</i> amplification of the catalase activity in erythrocytes of γ-TPN-treated spontaneous hypertensive rats. Increase of binucleated cells was observed at the highest dose (100 mg/kg/day) only. Then, as a natural molecule, γ-TPN isn't free of damaging effects, and further investigations are needed to ensure limiting doses and regulation aspects.