Ramelteon Protects Intestinal Tissue Against Injury Caused by Methotrexate Via Showing Anti-apoptotic, Antiinflammatory and Antioxidant Properties

Objective:Methotrexate (MTX), a drug used in the treatment of autoimmune diseases and cancers, is a folic acid antagonist, but it has toxic effects on the gastrointestinal system (GIS). In this study, we examined the anti-inflammatory, antioxidant and anti-apoptotic effects of Ramelteon (RAM), a melatonin receptor agonist, on the MTX-induced toxicity in the intestinal tissue of rats.Methods:Thirty-two male Wistar albino rats were randomly divided into 4 groups; Control group, MTX group, MTX + RAM group, and RAM group. Single-dose 0.1 mL 20 mg/kg MTX, saline or 0.1 mL 10 mg/kg RAM orally was administered for 7 days. Animals were sacrificed at the end of 7 days after the last drug administration. Then, intestinal tissues were collected for biochemical, histopathological and immunohistochemical analyses.Results:While normal histological findings and biochemical parameters were observed in the control and RAM groups, in the MTX group, mononuclear cell infiltrations, hemorrhagic areas, degenerations in the submucosa and Lieberkuhn crypts were observed in the intestinal sections. Caspase-3 (Cas-3) and tumor necrosis factor-alpha (TNF-α) expressions, total oxidant status (TOS) and oxidative stress index (OSI) increased and total antioxidant status (TAS) decreased in the MTX group. RAM treatment decreased Cas-3 and TNF-α expressions, TOS, OSI levels and increased TAS levels.Conclusion:In this study, RAM showed anti-apoptotic, antioxidant and anti-inflammatory effects on MTX-induced toxicity in intestinal tissue. Therefore, it was suggested that RAM might be used in MTX-like toxicities to alleviate the side effects on the GIS

Could the long-term oncological safety of laparoscopic surgery in low-risk endometrial cancer also be valid for the high–intermediate-and high-risk patients? A multi-center turkish gynecologic oncology group study conducted with 2745 endometrial cancer cases. (trsgo-end-001)

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high–intermediate-and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high–intermediate-and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high–intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high–intermediateand high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high–intermediate- and high-risk endometrial cancer cases

Could the long-term oncological safety of laparoscopic surgery in low risk endometrial cancer be also valid for the high intermediate and high-risk patients? A multi-center Turkish gynecologic oncology group study conducted with 2745 endometrial cancer cases

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