PROTECTIVE EFFECT OF THE RAMELTEON, A MELATONIN AGONIST, AGAINST METHOTREXATE-INDUCED BONE-TOXICITY

Creative Commons License

Dinçer R., Baykal T., Doğuç D. K., Sarman E., Ceylan D.

SDÜ Tıp Fak Derg, cilt.29, sa.1, ss.53-58, 2022 (Scopus, TRDizin)

Özet

Objective
Methotrexate (MTX) used anti-metabolite, causes bone morbidity, including growth arrest and reduced bone mineral density. Melatonin, produced by the pineal gland, has also multiple positive effects in human bone cells, and positive effects on bone. Ramelteon (RMT) is a non-selective melatonin receptor agonist. In this study, we investigated whether ramelteon, a melatonin agonist, has a protective effect on MTX- induced bone toxicity.

Material and Methods
The rats divided into 4 groups, including Group 1 control group; Group 2 MTX group (20 mg/kg); Group 3 MTX+RMT (20 mg/kg + 10 mg/kg); Group 4 RMT (10 mg/kg). Oral ramelteon and intraperitoneal mtx were applied to the rats on the second day according to the groups. After 7 days, long bones were evaluated histologically with hematoxylin-eosin (HE) staining and immunohistochemically with Catepsin K and RUN X2 staining. For statistical analysis immunohistochemical scores of the groups were compared between the groups for this purpose, the Oneway ANOVA Duncan test was used by SPSS-22.00 package program.

Results
There was no significant difference between the control group (group I) and the experimental groups (group II-group III-group IV) in H&E staining of bone tissue sections (p>0.05). No positive staining was observed in any of the groups in CAT-K and RUN-X immunostaining (p>0.05).

Conclusion
It was showed that ramelteon has no anabolic function in bone turnover, histopathological and immunohistochemical, in bone toxicity induced by high-dose methotrexate on intact bone tissue.