Protection of Bortezomib-induced Neurotoxicity by Antioxidants

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-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cells were sorted for apoptotic cells (distributed into subG 1 phase) and cells at different stages of cell cycle (G 1 , S and G 2 /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: Bortezomibinduced neuropathy might be ameliorated by antioxidants.

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma

“…However, many reports, including ours, demonstrated that microtubule-targeted agents have potent neurotoxicity, adversely affecting the quality of life of patients on a long-term basis [ 61 , 62 , 63 , 64 ]. Iijima et al recently reported that carboplatin (CBDCA) was highly neurotoxic (TS N = 0.11 (3.2/27.9)), calculated using the data of Table 2 in Ref.…”

“…Iijima et al recently reported that carboplatin (CBDCA) was highly neurotoxic (TS N = 0.11 (3.2/27.9)), calculated using the data of Table 2 in Ref. [ 64 ]. It is urgent to investigate the neurotoxicity, extravasation as well as stomatitis of chromone derivatives, esters, and amides.…”

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell Carcinoma In Vitro

“…We have recently reported that several G 2 /M blockers such as taxanes paclitaxel [Taxol ® , the first microtubule stabilizing agent (24)] and docetaxel (25), and 3-styrylchromone derivatives [7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1benzopyran-4-one, 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7methoxy-4H-1-benzopyran-4-one] show very high TS values (>7267, >86122, 301 and 182, respectively) (26). However, many reports, including ours, demonstrated that microtubuletargeted agents have potent neurotoxicity, adversely affecting the quality of life of patients on a long-term basis (27)(28)(29)(30). We have also reported that doxorubicin induced very potent keratinocyte toxicity by inducing apoptosis, characterized by the loss of cell surface microvilli, chromatin condensation, nuclear fragmentation and caspase-3 activation (31).…”

Selenium attenuates bisphenol A incurred damage and apoptosis in mice testes by regulating mitogen‐activated protein kinase signalling

“…Antioxidants, viz. glutathione (GSH), weed out free radicals and other electrophilic compounds from the cells (Iijima et al., 2020), SOD transforms the harmful superoxide anions into molecular oxygen and hydrogen peroxide, CAT converts the hydrogen peroxide into harmless water and oxygen, GST coupled the GSH to several electrophilic compounds and defend the cells from excessive ROS generated by noxious xenobiotics, and therefore, all protected the cells/tissues from ROS attack and OS (Chalouati et al., 2019). The healthy cells maintain a high GSH‐to‐GSSG ratio.…”