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Iranian Journal of Basic Medical Sciences، جلد ۲۵، شماره ۱۰، صفحات ۱۱۸۳-۱۱۸۹
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عنوان انگلیسی Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity
چکیده انگلیسی مقاله Objective(s): Methotrexate (MTX) is a widely used chemotherapeutic agent that, however, is known to have serious side effects such as neurotoxicity. In the present study, we aimed to evaluate the possible favorable effects of ramelteon (RMLT) on MTX-induced cerebral toxicity. Materials and Methods: Thirty-two male Wistar albino rats were divided into four groups: Control group, MTX group (20 mg/kg MTX, IP, single dose), MTX+RMLT group (20 mg/kg MTX, IP, single dose + 10 mg/kg RMLT, by gavage, 7 days), and RMLT group (10 mg/kg RMLT, by gavage, 7 days). Results: In the MTX group, increased levels of total oxidant status (TOS) and oxidative stress index (OSI) levels and decreased levels of total antioxidant status (TAS) level were observed. RMLT significantly reversed oxidative stress parameters. Real-time PCR analysis revealed that MTX increased the expressions of Beclin-1 and autophagy-related gene 12 (ATG12). These expressions were significantly decreased by RMLT. Vacuolar changes, apoptotic cells, and inflammatory cell infiltration induced by MTX were ameliorated by RMLT treatment. Increased tumor necrosis factor-α (TNF- α) and Caspase-3 activities induced by MTX were returned to their normal levels by RMLT. Conclusion: All our results demonstrate that RMLT alleviates the harmful effects of MTX on the cerebral cortex tissue. Therefore, RMLT may be considered for supportive therapy for preventing side effects of MTX in patients needing MTX therapy.
کلیدواژه‌های انگلیسی مقاله Apoptosis, Autophagy, Cerebral toxicity, Inflammation, Methotrexate, Oxidative stress, Ramelteon
نویسندگان مقاله | Rahime Aslankoc
Süleyman Demirel University, Faculty of Medicine, Department of Physiology, Isparta, Turkey


| Mehtap Savran
Süleyman Demirel University, Faculty of Medicine, Department of Pharmacology, Isparta, Turkey


| Duygu Kumbul Doğuç
Süleyman Demirel University, Faculty of Medicine, Department of Biochemistry, Isparta, Turkey


| Murat Sevimli
Süleyman Demirel University, Faculty of Medicine, Department of Histology and Embryology, Isparta, Turkey


| Hale Tekin
Süleyman Demirel University, Graduate School of Natural and Applied Sciences, Department of Bioengineering, Isparta, Turkey


| Mine Kaynak
Süleyman Demirel University, Faculty of Medicine, Department of Pharmacology, Isparta, Turkey
نشانی اینترنتی https://ijbms.mums.ac.ir/article_21026.html
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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