Protective efficacy of ramelteon on methotrexate-induced DNA damage

Abstract

Ramelteon (RMLT) is a melatonin receptor agonist that it has antioxidative and anti-inflammatory effects associated with DNA damage through different mechanisms of action. In this regard, we investigated the potential usefulness of RMLT as a protective agent against methotrexate (MTX)-induced DNA damage. Four groups were constituted from 32 Wistar albino rats: Negative control, RMLT, MTX, and MTX + RMLT. Twenty mg/kg MTX (i.p., single dose) and RMLT 10 mg/kg (oral, 7 days) was administered. Comet assay was used and the parameter %TailDNA was used to detect DNA damage. %TailDNA was 4.90 ± 0.19 in the control group, 7.85 ± 0.33 in the MTX group, 5.49 ± 0.24 in the RMLT group, and 5.86 ± 0.23 in the MTX + RMLT group. While there was a significant increase in DNA damage in the MTX-treated group compared to the control group, there was a significant reduction in DNA damage in the MTX + RMLT group, compared to the MTX group (p < 0.001). In conclusion, it was observed that combined treatment with RMLT significantly reduced MTX-induced DNA damage.

Graphical Abstract

HIGHLIGHTS

• Investigate the possible protective effect of RMLT against DNA damage caused by MTX using the comet method.

• The DNA damage of RMLT treated group was significantly reduced compared to group and MTX group. (p < 0.001).

• Combined treatment with MTX significantly reduces MTX-induced DNA damage.

Keywords:

• Comet assay
• Genotoxicity
• Melatonin analogue
• Melatonin receptor agonist
• Ramelteon

Acknowledgements

We would like to thank Süleyman Demirel University for providing financial support.

Ethical approval

This research prioritized animal welfare throughout all experimental stages. Ethical approval was obtained from the Süleyman Demirel University Animal Experiments Local Ethics Committee with decision number of 06/10 on 11.09.2020.

Authors’ contributions

Gülçin Yavuz Türel: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Resources, Validation, Supervision, Visualization, Writing - original draft. Pınar Aslan Koşar: Methodology, Investigation, Resources, Visualization, Writing – review & editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported in part by Süleyman Demirel University Scientific Research Projects Coordination Unit under grant TSG-2020–8134.