Protective effect of a mechanistic target of rapamycin inhibitor on an in vivo model ofcisplatin-induced ovarian gonadotoxicity
| Autor: | Kyoko Kasahara, Shoji Kaku, Luyi Zheng, Shunichiro Tsuji, Fuminori Kimura, Akie Takebayashi, Yuji Tanaka, Takashi Murakami |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cisplatin Cisplatin Injection Everolimus General Veterinary biology business.industry General Medicine Pharmacology Antral follicle General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine In vivo 030220 oncology & carcinogenesis biology.protein Medicine Animal Science and Zoology business Ovarian reserve Mechanistic target of rapamycin PI3K/AKT/mTOR pathway medicine.drug |
| Zdroj: | Experimental Animals. 67:493-500 |
| ISSN: | 1881-7122 1341-1357 |
| DOI: | 10.1538/expanim.18-0042 |
| Popis: | This study aimed to evaluate the protective effect of everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, on cisplatin chemotherapy-induced ovarian toxicity. Eighty sexually mature, virgin, female, 7-week-old C57BL/6J mice were divided into four groups: control, cisplatin (Cis), everolimus (mTORi), and everolimus plus cisplatin (mTORi+Cis). Mice in the Cis and mTORi+Cis groups were intraperitoneally injected with 2 mg/kg of cisplatin for 15 d. Mice in the mTORi and mTORi+Cis groups were orally administered 2.5 mg/kg of everolimus for 29 d, from one week before the first cisplatin injection to one week after the last cisplatin injection. Histological examinations were performed 24 h after the last everolimus administration. The primordial, primary, and antral follicles were significantly depleted in the Cis group compared with that in the control group, confirming the gonadotoxicity of cisplatin. The number of primordial, secondary, and antral follicles was significantly higher in the mTORi+Cis group than in the Cis group, thereby displaying the effect of mTORi-treatment on ovarian protection. Primordial, secondary, and antral follicle counts were similar in the mTORi+Cis and the control groups. The results of this study indicate a protective effect of an mTOR inhibitor against cisplatin chemotherapy-induced gonadotoxicity in the ovarian reserve in an in vivo mouse model. |
| Databáze: | OpenAIRE |
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