Yosuke Iijima1, Kenjiro Bandow2, Shigeru Amano3, Motohiko Sano4, Shunsuke Hino5, Takahiro Kaneko5, Norio Horie5, Hiroshi Sakagami6. 1. Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan yoiijima@saitama-med.ac.jp sakagami@dent.meikai.ac.jp. 2. Division of Biochemistry, Meikai University School of Dentistry, Sakado, Japan. 3. Division of Microbiology, Meikai University School of Dentistry, Sakado, Japan. 4. Division of Applied Pharmaceutical Education and Research, Hoshi University, Tokyo, Japan. 5. Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan. 6. Meikai University Research Institute of Odontology (M-RIO), Sakado, Japan yoiijima@saitama-med.ac.jp sakagami@dent.meikai.ac.jp.
Abstract
BACKGROUND/AIM: Although chemotherapy agents, such as oxaliplatin, cisplatin, paclitaxel and bortezomib frequently cause severe peripheral neuropathy, very few studies have reported the effective strategy to prevent this side effect. In this study, we first investigated whether these drugs show higher neuropathy compared to a set of 15 other anticancer drugs, and then whether antioxidants, such as sodium ascorbate, N-acetyl-L-cysteine, and vitamin B12 have any protective effect against them. MATERIALS AND METHODS: Rat PC12 cells were induced to differentiate into neuronal cells by repeated overlay of serum-free medium supplemented with nerve growth factor. The cytotoxic levels of anticancer drugs against four human oral squamous cell carcinoma cell lines, three normal oral cells, and undifferentiated and differentiated PC12 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cells were sorted for apoptotic cells (distributed into subG1 phase) and cells at different stages of cell cycle (G1, S and G2/M). RESULTS: All 19 anticancer drugs showed higher cytotoxicity against PC12 compared to oral normal cells. Among them, bortezomib showed the highest cytotoxicity against both undifferentiated and differentiated PC12 cell and, committed them to undergo apoptosis. Sodium ascorbate and N-acetyl-L-cysteine, but not vitamin B12, completely reversed the cytotoxicity of bortezomib. CONCLUSION: Bortezomib-induced neuropathy might be ameliorated by antioxidants. Copyright
BACKGROUND/AIM: Although chemotherapy agents, such as oxaliplatin, cisplatin, paclitaxel and bortezomib frequently cause severe peripheral neuropathy, very few studies have reported the effective strategy to prevent this side effect. In this study, we first investigated whether these drugs show higher neuropathy compared to a set of 15 other anticancer drugs, and then whether antioxidants, such as sodium ascorbate, N-acetyl-L-cysteine, and vitamin B12 have any protective effect against them. MATERIALS AND METHODS:Rat PC12 cells were induced to differentiate into neuronal cells by repeated overlay of serum-free medium supplemented with nerve growth factor. The cytotoxic levels of anticancer drugs against four human oral squamous cell carcinoma cell lines, three normal oral cells, and undifferentiated and differentiated PC12 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cells were sorted for apoptotic cells (distributed into subG1 phase) and cells at different stages of cell cycle (G1, S and G2/M). RESULTS: All 19 anticancer drugs showed higher cytotoxicity against PC12 compared to oral normal cells. Among them, bortezomib showed the highest cytotoxicity against both undifferentiated and differentiated PC12 cell and, committed them to undergo apoptosis. Sodium ascorbate and N-acetyl-L-cysteine, but not vitamin B12, completely reversed the cytotoxicity of bortezomib. CONCLUSION:Bortezomib-induced neuropathy might be ameliorated by antioxidants. Copyright
Authors: Praveen K Roayapalley; Jonathan R Dimmock; Lisett Contreras; Karol S Balderrama; Renato J Aguilera; Hiroshi Sakagami; Shigeru Amano; Rajendra K Sharma; Umashankar Das Journal: Molecules Date: 2021-11-25 Impact factor: 4.927
Authors: Mohamed A A Orabi; Heba M A Khalil; Mohamed E Abouelela; Dalia Zaafar; Yasmine H Ahmed; Reham A Naggar; Hamad S Alyami; El-Shaymaa Abdel-Sattar; Katsuyoshi Matsunami; Dalia I Hamdan Journal: Pharmaceuticals (Basel) Date: 2021-12-14