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Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling.
Toxicol Appl Pharmacol. 2017 08 15; 329:128-139.TA

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 ERK and NF-κB signaling pathways. Galangin might be a potential adjuvant for clinical cisplatin therapy.

Authors+Show Affiliations

Department of Bioindustry Technology, Da-Yeh University, Taiwan, Republic of China; Department of Neurology, Taoyuan General Hospital, Ministry of Health and Welfare, Executive Yuan, Taiwan, Republic of China.Department of Bioindustry Technology, Da-Yeh University, Taiwan, Republic of China.Department of Biomedical Sciences, Chung Shan Medical University, Taiwan, Republic of China.Department of Biomedical Sciences, Chung Shan Medical University, Taiwan, Republic of China.Department of Biomedical Sciences, Chung Shan Medical University, Taiwan, Republic of China.Department of Biomedical Sciences, Chung Shan Medical University, Taiwan, Republic of China.Department of Biomedical Sciences, Chung Shan Medical University, Taiwan, Republic of China.Department of Biomedical Sciences, Chung Shan Medical University, Taiwan, Republic of China; Department of Medical Research, Chung Shan Medical University Hospital, Taiwan, Republic of China. Electronic address: wangsh@csmu.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28558962

Citation

Huang, Yu-Ching, et al. "Galangin Ameliorates Cisplatin-induced Nephrotoxicity By Attenuating Oxidative Stress, Inflammation and Cell Death in Mice Through Inhibition of ERK and NF-kappaB Signaling." Toxicology and Applied Pharmacology, vol. 329, 2017, pp. 128-139.
Huang YC, Tsai MS, Hsieh PC, et al. Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. Toxicol Appl Pharmacol. 2017;329:128-139.
Huang, Y. C., Tsai, M. S., Hsieh, P. C., Shih, J. H., Wang, T. S., Wang, Y. C., Lin, T. H., & Wang, S. H. (2017). Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. Toxicology and Applied Pharmacology, 329, 128-139. https://doi.org/10.1016/j.taap.2017.05.034
Huang YC, et al. Galangin Ameliorates Cisplatin-induced Nephrotoxicity By Attenuating Oxidative Stress, Inflammation and Cell Death in Mice Through Inhibition of ERK and NF-kappaB Signaling. Toxicol Appl Pharmacol. 2017 08 15;329:128-139. PubMed PMID: 28558962.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling. AU - Huang,Yu-Ching, AU - Tsai,Ming-Shiun, AU - Hsieh,Pei-Chi, AU - Shih,Jheng-Hong, AU - Wang,Tsu-Shing, AU - Wang,Yi-Chun, AU - Lin,Ting-Hui, AU - Wang,Sue-Hong, Y1 - 2017/05/27/ PY - 2017/02/22/received PY - 2017/05/21/revised PY - 2017/05/26/accepted PY - 2017/6/1/pubmed PY - 2017/8/2/medline PY - 2017/6/1/entrez KW - Cisplatin nephrotoxicity KW - ERK KW - Galangin KW - Inflammation KW - NF-κB KW - Oxidative stress SP - 128 EP - 139 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 329 N2 - 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. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/28558962/Galangin_ameliorates_cisplatin_induced_nephrotoxicity_by_attenuating_oxidative_stress_inflammation_and_cell_death_in_mice_through_inhibition_of_ERK_and_NF_kappaB_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(17)30240-5 DB - PRIME DP - Unbound Medicine ER -