MELATONİN AGONİSTİ OLAN RAMELTEONUN METOTREKSAT KAYNAKLI KEMİK TOKSİSİTESİNE KARŞI KORUYUCU ETKİSİ

Abstract

Amaç Metotreksat (MTX) büyüme durması ve kemik mineral yoğunluğunun azalması dahil olmak üzere kemik morbiditesine neden olan anti-metabolittir. Epifiz bezi tarafından üretilen melatonin, insan kemik hücrelerinde de birçok olumlu etkiye ve kemik üzerinde olumlu etkilere sahiptir. Ramelteon (RMT), seçici olmayan bir melatonin reseptör agonistidir. Bu çalışmada, bir melatonin agonisti olan ramelteonun MTX kaynaklı kemik toksisitesi üzerinde koruyucu bir etkisinin olup olmadığını araştırdık. Gereç ve Yöntem Sıçanlar Grup 1 kontrol grubu olmak üzere 4 gruba ayrıldı; Grup 2 MTX grubu (20 mg/kg); Grup 3 MTX+RMT (20 mg/kg + 10 mg/kg); Grup 4 RMT (10 mg/kg). Ratlara gruplara göre ikinci gün oral ramelteon ve intraperitoneal mtx uygulandı. 7 gün sonra uzun kemikler hematoksilen-eozin (HE) boyama ile histolojik olarak ve Catepsin K ve RUN X2 boyama ile immünohistokimyasal olarak değerlendirildi. İstatistiksel analiz için grupların immünhistokimyasal skorları gruplar arasında karşılaştırıldı, bu amaçla SPSS-22.00 paket programı ile Oneway ANOVA Duncan testi kullanıldı. Bulgular Kemik doku kesitlerinin H&E boyamasında kontrol grubu (grup I) ile deney grupları (grup II-grup III-grup IV) arasında anlamlı bir fark yoktu (p>0.05). CAT-K ve RUN-X immün boyamasında grupların hiçbirinde pozitif boyanma gözlenmedi (p>0.05). Sonuç Ramelteonun, sağlam kemik dokusu üzerinde yüksek doz metotreksatın neden olduğu kemik toksisitesinde, kemik döngüsünde, histopatolojik ve immünohistokimyasal olarak anabolik bir işlevi olmadığı gösterilmiştir.

Keywords

• Metotreksat
• Ramelteon
• Melatonin
• Katepsin-K
• RUNX2

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

Abstract

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 MTXinduced 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.

Keywords

• METHOTREXATE
• RAMELTEON
• MELATONIN
• RUNX2
• Catepsin K

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