Toxicogenetic profile of the monoterpene alpha-terpineol on normal and tumor eukaryotic cells

Abstract

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 μg/mL), Artemia salina (6.25–400 μg/mL), Allium cepa (10, 50, and 100 μg/mL), comet assay (100, 200, and 500 μg/mL), cytokinesis-block micronucleus (100, 250, and 500 μg/mL), confocal microscopy for apoptosis quantification (100 and 500 μg/mL), hemolysis and Saccharomyces cerevisiae central disk test (10, 35, and 75 μg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16–F10 cells rather than macrophages. For A. salina test, alpha-terpineol showed LC₅₀ of 68.29 and 76.36 μg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 μg/mL, but it caused neither hemolysis, oxidative damage on the S. cerevisiae nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells.

Keywords:

• Essential oils
• alpha-terpineol
• toxicology
• genotoxicity
• antitumor activity

Acknowledgements

The authors thank the Federal University of Piauí and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support. Paulo Michel Pinheiro Ferreira is also grateful to the public Brazilian agency CNPq for his personal scholarship (#304803/2022-7).

Author contributions

Conceptualization, H.A.N. and J.M.C.S.; methodology, H.A.N., J.M.C.S., A.A.C.M.C., P.M.P.F., A.N.M., and J.C.R.G.; software, J.M.C.S and J.C.R.G.; validation, J.M.C.S., A.A.C.M.C., P.M.P.F., and A.N.M.; formal analysis, H.A.N., M.G.F., M.L.L.B.N., K.G.M., L. S.C., and A.R.S.P.; investigation, H.A.N., S.B.C.F., F.A.B., M.G.F., F.C.C.S., M.L.L.B.N., K.G.M., L.S.C., and A.R.S.P.; resources, J.M.C.S., A.A.C.M.C., F.C.C.S., and H.A.N.; data curation, H.A.N., F.C.C.S., and J.M.C.S; writing-original draft preparation, H.A.N., M.G.F., and K.G.M.; writing-review and editing, H.A.N., J.M.C.S., and P.M.P.F; visualization, P.M.P.F., A.N.M., and J.C.R.G.; supervision, A.A.C.M.C. and J.M.C.S.; project administration, L.O.L., A.A.C.M.C., and J.M.C.S.

Disclosure statement

There are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Data availability statement

All data and materials are available upon request.

Additional information

Funding

The authors thank the Federal University of Piauí and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support. Paulo Michel Pinheiro Ferreira is also grateful to the public Brazilian agency CNPq for his personal scholarship [#304803/2022-7].