1. A study on Wistar Albino rats: investigating protective role of ramelteon on liver damage caused by methotrexate
- Author
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Şakir Pekgöz, İlter İlhan, Ali Mustafaoğlu, Meltem Özgöçmen, Halil Asci, and Hatice Kübra Doğan
- Subjects
Health, Toxicology and Mutagenesis ,Antineoplastic drug ,Interleukin-1beta ,Ramelteon ,Pharmacology ,Toxicology ,Antioxidants ,medicine ,Animals ,Sirtuins ,Aspartate Aminotransferases ,Liver damage ,Rats, Wistar ,Hematoxylin ,Adverse effect ,Chemical Health and Safety ,Caspase 3 ,business.industry ,Public Health, Environmental and Occupational Health ,Alanine Transaminase ,General Medicine ,Oxidants ,Rats ,Oxidative Stress ,Methotrexate ,Liver ,Chemical and Drug Induced Liver Injury ,Tumor Suppressor Protein p53 ,business ,medicine.drug - Abstract
Methotrexate is an important immunosuppressive and antineoplastic drug and is widely used for treatment. However, hepatotoxicity is one of the major adverse effects of methotrexate. In this study, it was aimed to investigate whether ramelteon has a possible protective effect on hepatotoxicity induced by methotrexate. Thirty-two Wistar albino rats were equally divided into four groups: control, methotrexate, methotrexate + ramelteon, and ramelteon. Following a single dose of 20 mg/kg, methotrexate (i.p.), either saline or ramelteon 10 mg/kg (orally) was administered for 7 days. After treatment, animals were sacrificed, and histopathological analyses were evaluated with Hematoxylin-eosin (H-E), immunohistological analyses were evaluated with Interleukin-1 Beta (IL-1 beta) and Caspase 3 (CAS-3), biochemical analyzes were evaluated with Total Oxidant Status (TOS), Total antioxidants status (TAS), Oxidative Stress Index (OSI), aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, at last genetical analyses were evaluated with Sirtuin-1 (SIRT-1) - P53 gene expressions. In the control and ramelteon groups, normal histological structures were observed, while histopathological findings were observed in the methotrexate group. Increasing levels of IL-1 beta staining, CAS-3 staining, p53 gene expression, TOS, OSI, AST and ALT were observed in methotrexate group while were observed decreasing levels of TAS and SIRT-1 gene expression (p < 0.05). However, ramelteon reduced the increased findings in methotrexate-induced hepatotoxicity (p < 0.05). The results of the present study showed that ramelteon protects against methotrexate induced hepatotoxicity in rats via SIRT-1 signaling by histological, immunohistological, biochemical and genetical analyses.
- Published
- 2021