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Title: Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling

Abstract

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers. However, cisplatin can induce nephrotoxicity and neurotoxicity, limiting its dosage and usage. Galangin, a natural flavonol, has been found to exhibit anti-oxidant and anti-inflammatory effects in vivo. Here, we investigated the effects of galangin on cisplatin-induced acute kidney injury (AKI) and its molecular mechanisms in mice. Galangin administration reduced the cisplatin-induced oxidative stress by decreasing renal MDA and 3-NT formations. Galangin administration also increased renal anti-oxidative enzyme activities (SOD, GPx, and CAT) and GSH levels depleted by cisplatin. Furthermore, galangin administration inactivated stress-induced Nrf2 protein and its downstream products, HO-1 and GCLC. In terms of the inflammatory response, galangin administration reduced IκBα phosphorylation, NF-κB phosphorylation and nuclear translocation, and then inhibited cisplatin-induced secretions of pro-inflammatory TNF-α, IL-1β and IL-6. In addition, cisplatin-induced ERK and p38 phosphorylations were inhibited by galangin administration. In terms of cell death, galangin administration reduced levels of p53, pro-apoptotic Bax and activated caspase-3 to inhibit the cisplatin-induced apoptosis. Galangin administration also reduced the expression levels of RIP1 and RIP3 to inhibit cisplatin-induced RIP1/RIP3-dependent necroptosis. Therefore, galangin administration significantly ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation, and cell death through inhibitions of ERKmore » and NF-κB signaling pathways. Galangin might be a potential adjuvant for clinical cisplatin therapy. - Highlights: • Galangin alleviates cisplatin-induced acute kidney injury through ERK and NF-kappaB signaling pathways. • Galangin reduces cisplatin-induced oxidative stress and inflammatory response. • Galangin suppresses cisplatin-induced cell death, apoptosis and necroptosis.« less

Authors:
 [1];  [2];  [1]; ; ; ; ;  [3];  [3];  [2]
  1. Department of Bioindustry Technology, Da-Yeh University, Taiwan (China)
  2. (China)
  3. Department of Biomedical Sciences, Chung Shan Medical University, Taiwan (China)
Publication Date:
OSTI Identifier:
22722893
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 329; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; ENZYME ACTIVITY; INFLAMMATION; INHIBITION; KIDNEYS; MICE; OXIDATION; PHOSPHORUS 38; PHOSPHORYLATION; SIGNALS; STRESSES; SUPEROXIDE DISMUTASE

Citation Formats

Huang, Yu-Ching, Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Executive Yuan, Taiwan, Tsai, Ming-Shiun, Hsieh, Pei-Chi, Shih, Jheng-Hong, Wang, Tsu-Shing, Wang, Yi-Chun, Lin, Ting-Hui, Wang, Sue-Hong, and Department of Medical Research, Chung Shan Medical University Hospital, Taiwan. Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.05.034.
Huang, Yu-Ching, Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Executive Yuan, Taiwan, Tsai, Ming-Shiun, Hsieh, Pei-Chi, Shih, Jheng-Hong, Wang, Tsu-Shing, Wang, Yi-Chun, Lin, Ting-Hui, Wang, Sue-Hong, & Department of Medical Research, Chung Shan Medical University Hospital, Taiwan. Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. United States. doi:10.1016/J.TAAP.2017.05.034.
Huang, Yu-Ching, Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Executive Yuan, Taiwan, Tsai, Ming-Shiun, Hsieh, Pei-Chi, Shih, Jheng-Hong, Wang, Tsu-Shing, Wang, Yi-Chun, Lin, Ting-Hui, Wang, Sue-Hong, and Department of Medical Research, Chung Shan Medical University Hospital, Taiwan. Tue . "Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling". United States. doi:10.1016/J.TAAP.2017.05.034.
@article{osti_22722893,
title = {Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling},
author = {Huang, Yu-Ching and Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Executive Yuan, Taiwan and Tsai, Ming-Shiun and Hsieh, Pei-Chi and Shih, Jheng-Hong and Wang, Tsu-Shing and Wang, Yi-Chun and Lin, Ting-Hui and Wang, Sue-Hong and Department of Medical Research, Chung Shan Medical University Hospital, Taiwan},
abstractNote = {Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers. However, cisplatin can induce nephrotoxicity and neurotoxicity, limiting its dosage and usage. Galangin, a natural flavonol, has been found to exhibit anti-oxidant and anti-inflammatory effects in vivo. Here, we investigated the effects of galangin on cisplatin-induced acute kidney injury (AKI) and its molecular mechanisms in mice. Galangin administration reduced the cisplatin-induced oxidative stress by decreasing renal MDA and 3-NT formations. Galangin administration also increased renal anti-oxidative enzyme activities (SOD, GPx, and CAT) and GSH levels depleted by cisplatin. Furthermore, galangin administration inactivated stress-induced Nrf2 protein and its downstream products, HO-1 and GCLC. In terms of the inflammatory response, galangin administration reduced IκBα phosphorylation, NF-κB phosphorylation and nuclear translocation, and then inhibited cisplatin-induced secretions of pro-inflammatory TNF-α, IL-1β and IL-6. In addition, cisplatin-induced ERK and p38 phosphorylations were inhibited by galangin administration. In terms of cell death, galangin administration reduced levels of p53, pro-apoptotic Bax and activated caspase-3 to inhibit the cisplatin-induced apoptosis. Galangin administration also reduced the expression levels of RIP1 and RIP3 to inhibit cisplatin-induced RIP1/RIP3-dependent necroptosis. Therefore, galangin administration significantly ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation, and cell death through inhibitions of ERK and NF-κB signaling pathways. Galangin might be a potential adjuvant for clinical cisplatin therapy. - Highlights: • Galangin alleviates cisplatin-induced acute kidney injury through ERK and NF-kappaB signaling pathways. • Galangin reduces cisplatin-induced oxidative stress and inflammatory response. • Galangin suppresses cisplatin-induced cell death, apoptosis and necroptosis.},
doi = {10.1016/J.TAAP.2017.05.034},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 329,
place = {United States},
year = {2017},
month = {8}
}