EVALUATION OF THE PROTECTIVE EFFECT OF RAMELTEON IN METHOTREXATE INDUCED NEPHROTOXICITY

Authors : Halil İbrahim BÜYÜKBAYRAM, Dilek BAYRAM, Hatice Kübra DOĞAN

Pages : 155-162

Doi:10.17343/sdutfd.1114352

View : 46 | Download : 37

Publication Date : 2023-06-22

Article Type : Research Paper

Abstract :Objective Methotrexate insert ignore into journalissuearticles values(MTX);, which is used as an immunosuppressive and anticancer drug, causes serious toxic side effects in many organs, including the kidney. Activation of apoptotic pathways through oxidative stress is involved in the mechanism of MTX mediated nephrotoxicity. In our study, we investigated the protective effects of ramelteon insert ignore into journalissuearticles values(RML);, an analogue of melatonin, whose antioxidant and antiapoptotic properties are well known, on MTX nephrotoxicity. Material and Method 32 rats were divided into 4 groups as Control, MTX, MTX+RML and RML. According to the groups, saline or RML insert ignore into journalissuearticles values(10 mg/kg); was administered by oral gavage for 7 days, and on the 2nd day, 20 mg of MTX or the same volume of saline was administered intraperitoneally according to the groups. At the end of the experiment, the rats were sacrificed and kidney tissues were examined histopathologically with Hematoxylin-Eosin insert ignore into journalissuearticles values(HE); staining and immunohistochemically insert ignore into journalissuearticles values(IHC); with caspase-3 and TNF-α staining. In addition, serum BUN, creatinine levels were measured, kidney Total Oxidant and Antioxidant Status insert ignore into journalissuearticles values(TAS, TOS); levels were studied and Oxidative Stress Index insert ignore into journalissuearticles values(OSI); was calculated. Results Creatinine, TOS and OSI levels in the MTX group were found to be significantly higher than in the control group. In HE staining, tissue damage was significantly higher in MTX group compared to the control group, and cas-3 and TNF-α staining levels were increased in IHC staining. These findings were found to be reversed in the MTX+RML group. Conclusion We show that RML treatment improves the findings of MTX-induced nephrotoxicity. RML may be a promising drug in MTX nephrotoxicity.
Keywords : Apoptoz, İlaca bağlı nefrotoksisite, Melatonin analogları, Oksidatif stres