Galangin ameliorates cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammation and cell death in mice through inhibition of ERK and NF-kappaB signaling
| Autor: | Ming-Shiun Tsai, Yu-Ching Huang, Pei-Chi Hsieh, Tsu-Shing Wang, Jheng-Hong Shih, Ting-Hui Lin, Sue-Hong Wang, Yi-Chun Wang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway NF-E2-Related Factor 2 Glutamate-Cysteine Ligase Necroptosis Anti-Inflammatory Agents Apoptosis Pharmacology Kidney Toxicology medicine.disease_cause Antioxidants Nephrotoxicity 03 medical and health sciences chemistry.chemical_compound Malondialdehyde medicine Animals Phosphorylation Extracellular Signal-Regulated MAP Kinases Flavonoids Mice Inbred BALB C Dose-Response Relationship Drug business.industry NF-kappa B Membrane Proteins Acute Kidney Injury Galangin Disease Models Animal Oxidative Stress IκBα 030104 developmental biology GCLC chemistry Cytoprotection Immunology Cytokines Tyrosine Cisplatin Inflammation Mediators Apoptosis Regulatory Proteins business Heme Oxygenase-1 Oxidative stress Signal Transduction |
| Zdroj: | Toxicology and Applied Pharmacology. 329:128-139 |
| ISSN: | 0041-008X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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