TY  - JOUR
T1  - EVALUATION OF THE PROTECTIVE EFFECT OF RAMELTEON IN METHOTREXATE INDUCED NEPHROTOXICITY
TT  - METOTREKSAT ARACILI NEFROTOKSİSİTEDE RAMELTEONUN KORUYUCU ETKİSİNİN DEĞERLENDİRİLMESİ
AU  - Büyükbayram, Halil İbrahim
AU  - Bayram, Dilek
AU  - Doğan, Hatice Kübra
PY  - 2023
DA  - June
Y2  - 2022
DO  - 10.17343/sdutfd.1114352
JF  - Medical Journal of Süleyman Demirel University
JO  - Med J SDU
PB  - Süleyman Demirel University
WT  - DergiPark
SN  - 1300-7416
SP  - 155
EP  - 162
VL  - 30
IS  - 2
LA  - en
AB  - ObjectiveMethotrexate (MTX), which is used as animmunosuppressive and anticancer drug, causesserious toxic side effects in many organs, includingthe kidney. Activation of apoptotic pathways throughoxidative stress is involved in the mechanism of MTXmediated nephrotoxicity. In our study, we investigatedthe protective effects of ramelteon (RML), an analogueof melatonin, whose antioxidant and antiapoptoticproperties are well known, on MTX nephrotoxicity.Material and Method32 rats were divided into 4 groups as Control, MTX,MTX+RML and RML. According to the groups, salineor RML (10 mg/kg) was administered by oral gavage for7 days, and on the 2nd day, 20 mg of MTX or the samevolume of saline was administered intraperitoneallyaccording to the groups. At the end of the experiment,the rats were sacrificed and kidney tissues wereexamined histopathologically with Hematoxylin-Eosin(HE) staining and immunohistochemically (IHC) withcaspase-3 and TNF-α staining. In addition, serum BUN,creatinine levels were measured, kidney Total Oxidantand Antioxidant Status (TAS, TOS) levels were studiedand Oxidative Stress Index (OSI) was calculated.ResultsCreatinine, TOS and OSI levels in the MTX groupwere found to be significantly higher than in the controlgroup. In HE staining, tissue damage was significantlyhigher in MTX group compared to the control group,and cas-3 and TNF-α staining levels were increased inIHC staining. These findings were found to be reversedin the MTX+RML group.ConclusionWe show that RML treatment improves the findings ofMTX-induced nephrotoxicity. RML may be a promisingdrug in MTX nephrotoxicity.
KW  - Melatonin analogs
KW  - drug induced nephrotoxicity
KW  - oxidative stress
KW  - apoptosis
N2  - Amaçİmmünsüpresif ve antikanser olarak kullanılan Metotreksat(MTX), böbrek dahil birçok organda ciddi toksikyan etkilere neden olmaktadır. Mtx aracılı nefrotoksisiteninmekanizmasında oksidatif stres üzerindenapoptotik yolakların aktive olması yer almaktadır.Çalışmamızda antioksidan ve antiapoptotik özellikleriiyi bilinen melatonin’in analoglarından Ramelteon’un(RML) MTX nefrotoksisitesindeki koruyucu etkileriniaraştırdık.Gereç ve Yöntem32 adet sıçan Kontrol, MTX, MTX+RML ve RML olmaküzere 4 gruba ayrıldı. Gruplara göre 7 gün boyuncaoral gavajla salin (SF) ya da RML (10 mg/kg)uygulandı, 2. gün ise gruplara göre intraperitoneal20 mg MTX ya da aynı hacimde salin uygulandı. Deneysonunda ratlar sakrifiye edilerek böbrek dokularıHematoksilen-Eozin (HE) boyama ile histopatolojikolarak, caspase-3 ve TNF-α boyama ile immünohistokimyasal(İHC) olarak incelendi. Ayrıca serum BUN,kreatinin düzeyleri ölçüldü ve böbrek Total oksidan veantioksidan durum (TAS, TOS) düzeyleri çalışılarakOksidatif stres indeksi (OSİ) hesaplandı.BulgularMTX grubunda kreatinin, TOS ve OSİ düzeyleri Kontrolgrubuna göre anlamlı düzeyde yüksek saptandı.HE boyamada MTX grubunda Kontrol grubuna göreanlamlı düzeyde yüksek doku hasarı, İHC boyamadacas-3 ve TNF-α boyanma düzeylerinde artış saptandı.Bu bulguların MTX+RML grubunda geriye çevrildiğisaptandı.SonuçRML tedavisinin, MTX’in yol açtığı nefrotoksisiteyeilişkin bulguları iyileştirdiğini gösterdik. RML, MTXnefrotoksisitesinde umut vadeden bir ilaç olabilir.
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UR  - https://doi.org/10.17343/sdutfd.1114352
L1  - https://dergipark.org.tr/en/download/article-file/2418345
ER  -