Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model
Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemoth...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/7/1942 |
| _version_ | 1797562149738905600 |
|---|---|
| author | Makito Miyake Shunta Hori Yoshitaka Itami Yuki Oda Takuya Owari Tomomi Fujii Sayuri Ohnishi Yosuke Morizawa Daisuke Gotoh Yasushi Nakai Satoshi Anai Kazumasa Torimoto Nobumichi Tanaka Kiyohide Fujimoto |
| author_facet | Makito Miyake Shunta Hori Yoshitaka Itami Yuki Oda Takuya Owari Tomomi Fujii Sayuri Ohnishi Yosuke Morizawa Daisuke Gotoh Yasushi Nakai Satoshi Anai Kazumasa Torimoto Nobumichi Tanaka Kiyohide Fujimoto |
| author_sort | Makito Miyake |
| collection | DOAJ |
| description | Chemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks—(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice. |
| first_indexed | 2024-03-10T18:24:24Z |
| format | Article |
| id | doaj.art-1a7eb8df78c9499fa0a6ba48ca03023f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:24:24Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1a7eb8df78c9499fa0a6ba48ca03023f2023-11-20T07:06:20ZengMDPI AGCancers2072-66942020-07-01127194210.3390/cancers12071942Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse ModelMakito Miyake0Shunta Hori1Yoshitaka Itami2Yuki Oda3Takuya Owari4Tomomi Fujii5Sayuri Ohnishi6Yosuke Morizawa7Daisuke Gotoh8Yasushi Nakai9Satoshi Anai10Kazumasa Torimoto11Nobumichi Tanaka12Kiyohide Fujimoto13Department of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Diagnostic Pathology, Nara Medical University School of Medicine, Nara 634-8521, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanDepartment of Urology, Nara Medical University School of Medicine, Nara 634-8522, JapanChemotherapy-induced adverse effects can reduce the relative dose intensity and quality of life. In this study, we investigated the potential benefit of supplementary anamorelin and 5-aminolevulinic acid (5-ALA) as preventive interventions against a gemcitabine and cisplatin (GC) combination chemotherapy-induced adverse effects in a mouse model. Non-cancer-bearing C3H mice were randomly allocated as follows and treated for 2 weeks—(1) non-treated control, (2) oral anamorelin alone, (3) oral 5-ALA alone, (4) gemcitabine and cisplatin (GC) chemotherapy, (5) GC plus anamorelin, and (6) GC plus 5-ALA. GC chemotherapy significantly decreased body weight, food intake, skeletal muscle mass and induced severe gastric mucositis, which resulted in decreased ghrelin production and blood ghrelin level. The supplementation of oral anamorelin to GC chemotherapy successfully mitigated decrease of food intake during the treatment period and body weight loss at day 8. In addition, analysis of the resected muscles and stomach revealed that anamorelin suppressed chemotherapy-induced skeletal muscle atrophy by mediating the downregulation of forkhead box protein O-1 (FOXO1)/atrogin-1 signaling and gastric damage. Our findings suggest the preventive effect of anamorelin against GC combination chemotherapy, which was selected for patients with some types of advanced malignancies in clinical practice.https://www.mdpi.com/2072-6694/12/7/1942chemotherapyanamorelinurothelial cancerbladder neoplasmappetite lossmuscle atrophy |
| spellingShingle | Makito Miyake Shunta Hori Yoshitaka Itami Yuki Oda Takuya Owari Tomomi Fujii Sayuri Ohnishi Yosuke Morizawa Daisuke Gotoh Yasushi Nakai Satoshi Anai Kazumasa Torimoto Nobumichi Tanaka Kiyohide Fujimoto Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model Cancers chemotherapy anamorelin urothelial cancer bladder neoplasm appetite loss muscle atrophy |
| title | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
| title_full | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
| title_fullStr | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
| title_full_unstemmed | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
| title_short | Supplementary Oral Anamorelin Mitigates Anorexia and Skeletal Muscle Atrophy Induced by Gemcitabine Plus Cisplatin Systemic Chemotherapy in a Mouse Model |
| title_sort | supplementary oral anamorelin mitigates anorexia and skeletal muscle atrophy induced by gemcitabine plus cisplatin systemic chemotherapy in a mouse model |
| topic | chemotherapy anamorelin urothelial cancer bladder neoplasm appetite loss muscle atrophy |
| url | https://www.mdpi.com/2072-6694/12/7/1942 |
| work_keys_str_mv | AT makitomiyake supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT shuntahori supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT yoshitakaitami supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT yukioda supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT takuyaowari supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT tomomifujii supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT sayuriohnishi supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT yosukemorizawa supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT daisukegotoh supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT yasushinakai supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT satoshianai supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT kazumasatorimoto supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT nobumichitanaka supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel AT kiyohidefujimoto supplementaryoralanamorelinmitigatesanorexiaandskeletalmuscleatrophyinducedbygemcitabinepluscisplatinsystemicchemotherapyinamousemodel |