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In Vivo. 2018 Jul-Aug;32(4):745-752. doi: 10.21873/invivo.11303.

Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants.

Author information

1
Department of Oral Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo, Japan.
2
Meikai University Research Institute of Odontology, Meikai University School of Dentistry, Saitama, Japan.
3
Meikai University Research Institute of Odontology, Meikai University School of Dentistry, Saitama, Japan sakagami@dent.meikai.ac.jp.
4
Department of Traditional Chinese Medicine, Shanghai Ninth People's Hospital, Shanghai Jiatong University School of Medicine, Shanghai, P.R. China.
5
Division of Geriatric Dentistry, Meikai University School of Dentistry, Saitama, Japan.
6
Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.

Abstract

BACKGROUND/AIM:

In order to search for substances that reduce the neurotoxicity of paclitaxel, the sensitivity of differentiated rat neuronal PC12 cells to paclitaxel was compared to that of malignant and non-malignant cells, and the extent to which four antioxidants can alleviate paclitaxel-induced neurotoxicity was investigated.

MATERIALS AND METHODS:

Viability of cells was determined by the MTT method. Cytotoxicity was evaluated as the concentration that reduced cell viability by 50% (CC50). Tumor specificity of paclitaxel was determined as the ratio of CC50 against non-malignant cells to that against malignant cells.

RESULTS:

Paclitaxel was three-fold more cytotoxic towards human oral squamous cell carcinoma cell lines (Ca9-22, HSC-2, HSC-3. HSC-4) than human normal epithelial and mesenchymal (human gingival fibroblast, human periodontal ligament fibroblast, human pulp cell) normal cells, confirming its antitumor potential. However, paclitaxel at as low a concentration as 5 ng/ml significantly reduced neurite formation in nerve growth factor-induced differentiated PC12 cells, although complete killing of cells was not achieved even at 2,000-fold higher concentration (10 μM). Paclitaxel-induced neurotoxicity was enhanced with the prolongation of incubation time and reduction of inoculation cell density. Four antioxidants, namely docosahexaenoic acid, acetyl-L-carnitine hydrochloride, N-acetyl-L-cysteine and sodium ascorbate, only partially protected PC12 cells from paclitaxel-induced toxicity.

CONCLUSION:

The present study suggests the involvement of both oxidative and other mechanisms in paclitaxel-induced neurotoxicity.

KEYWORDS:

NGF; Neurotoxicity; PC12; anticancer drug; differentiation stage

PMID:
29936454
PMCID:
PMC6117766
DOI:
10.21873/invivo.11303
[Indexed for MEDLINE]
Free PMC Article

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