Alphalipoic Acid Prevents Oxidative Stress and Peripheral Neuropathy in Nab-Paclitaxel-Treated Rats through the Nrf2 Signalling Pathway
Joint Authors
Cai, Weimin
Sun, Hong
Guo, Xi
Wang, Ziteng
Wang, Peipei
Zhang, Zhe
Dong, Jihong
Zhuang, Rongyuan
Zhou, Yuhong
Ma, Guo
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-02-10
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Peripheral neuropathy is the major dose-limiting side effect of paclitaxel (PTX), affecting both the quality of life and the survival of cancer patients.
Nab-paclitaxel (nab-PTX) was developed to provide additional clinical benefits and overcome the safety drawbacks of solvent-based PTX.
However, the prevalence of peripheral neuropathy induced by nab-PTX was reported higher than that induced by solvent-based PTX.
Upon investigation, oxidative stress plays a major role in the toxicity of nab-PTX.
In order to assess if the antioxidant alphalipoic acid (α-LA) could prevent the nab-PTX-induced peripheral neuropathy, Sprague-Dawley (SD) rats were treated with three doses of α-LA (15, 30, and 60 mg/kg in normal saline, i.p., q.d.
(days 1-30)) and/or nab-PTX (7.4 mg/kg in normal saline, i.v., q.w.
(days 8, 15, and 22)).
Body weight and peripheral neuropathy were measured and assessed regularly during the study.
The assessment of peripheral neuropathy was performed by the von Frey and acetone tests.
A tumor xenograft model of pancreatic cancer was used to assess the impact of α-LA on the antitumor effect of nab-PTX.
Results showed that α-LA significantly ameliorated the peripheral neuropathy induced by nab-PTX (p<0.05) without promoting tumor growth or reducing the chemotherapeutic effect of nab-PTX in a tumor xenograft model.
Moreover, α-LA might significantly reverse the superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels altered by nab-PTX in the serum and the spinal cord of rats.
Furthermore, α-LA could reverse the mRNA and protein expressions of Nrf2 (nuclear factor erythroid 2-related factor 2) and three Nrf2-responsive genes (HO-1, γ-GCLC, and NQO1) altered by nab-PTX in the dorsal root ganglion (DRG) of rats.
In conclusion, our study suggests that α-LA could prevent oxidative stress and peripheral neuropathy in nab-PTX-treated rats through the Nrf2 signalling pathway without diminishing chemotherapeutic effect.
American Psychological Association (APA)
Sun, Hong& Guo, Xi& Wang, Ziteng& Wang, Peipei& Zhang, Zhe& Dong, Jihong…[et al.]. 2019. Alphalipoic Acid Prevents Oxidative Stress and Peripheral Neuropathy in Nab-Paclitaxel-Treated Rats through the Nrf2 Signalling Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1203093
Modern Language Association (MLA)
Sun, Hong…[et al.]. Alphalipoic Acid Prevents Oxidative Stress and Peripheral Neuropathy in Nab-Paclitaxel-Treated Rats through the Nrf2 Signalling Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1203093
American Medical Association (AMA)
Sun, Hong& Guo, Xi& Wang, Ziteng& Wang, Peipei& Zhang, Zhe& Dong, Jihong…[et al.]. Alphalipoic Acid Prevents Oxidative Stress and Peripheral Neuropathy in Nab-Paclitaxel-Treated Rats through the Nrf2 Signalling Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1203093
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203093