The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways
Abstract Cisplatin, a potent anticancer drug, is usually causing nephrotoxicity; limiting its therapeutic application and efficiency. Maltol may be used to prevent such toxic effect. The aim of this study was to investigate the underlying protective mechanisms of maltol on nephrotoxicity by cisplati...
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Nature Portfolio
2018
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oai:doaj.org-article:2ae4566f8538477387f5275278a4aaad2021-12-02T11:40:53ZThe protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways10.1038/s41598-018-34156-62045-2322https://doaj.org/article/2ae4566f8538477387f5275278a4aaad2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34156-6https://doaj.org/toc/2045-2322Abstract Cisplatin, a potent anticancer drug, is usually causing nephrotoxicity; limiting its therapeutic application and efficiency. Maltol may be used to prevent such toxic effect. The aim of this study was to investigate the underlying protective mechanisms of maltol on nephrotoxicity by cisplatin using a cisplatin-treated mouse model and a cellular toxicity model of HEK293 cells. The blood urea nitrogen (BUN), creatinine (CRE) and neutrophil gelatinase-associated lipocalin (NGAL) levels in mice were increased by cisplatin but decreased to normal ranges by maltol pretreatment (50 and 100 mg/kg) for ten days. Besides, maltol pretreatment decreased oxidative stress, lipid peroxidation and apoptosis in cisplatin-treated mice. The inhibitory action of maltol on inflammatory responses was achieved by reducing the expressions in NF-κB, IL-1β, iNOS, and TNF-α in the mice in vivo. Additionally, maltol restored the reduction of PI3K/Akt and mTOR levels by cisplatin through increasing AMPK expression in cisplatin-treated HEK293 cells. Maltol also suppressed the expression of Bax and caspase 3 by inhibiting the p53 activity in HEK293 cells. Overall, maltol may serve as a valuable potential drug to prevent cisplatin-induced nephrotoxicity, and the underlying molecular mechanisms of maltol action may involve intracellular AMPK/PI3K/Akt and p53 signaling pathways.Xiao-jie MiJin-gang HouZi WangYe HanShen RenJun-nan HuChen ChenWei LiNature PortfolioarticleMaltolNeutrophil Gelatinase-associated Lipocalin (NGAL)HEK293 CellsCisplatin-treated MiceCisplatin-induced Acute Kidney InjuryMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
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Maltol Neutrophil Gelatinase-associated Lipocalin (NGAL) HEK293 Cells Cisplatin-treated Mice Cisplatin-induced Acute Kidney Injury Medicine R Science Q |
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Maltol Neutrophil Gelatinase-associated Lipocalin (NGAL) HEK293 Cells Cisplatin-treated Mice Cisplatin-induced Acute Kidney Injury Medicine R Science Q Xiao-jie Mi Jin-gang Hou Zi Wang Ye Han Shen Ren Jun-nan Hu Chen Chen Wei Li The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways |
| description |
Abstract Cisplatin, a potent anticancer drug, is usually causing nephrotoxicity; limiting its therapeutic application and efficiency. Maltol may be used to prevent such toxic effect. The aim of this study was to investigate the underlying protective mechanisms of maltol on nephrotoxicity by cisplatin using a cisplatin-treated mouse model and a cellular toxicity model of HEK293 cells. The blood urea nitrogen (BUN), creatinine (CRE) and neutrophil gelatinase-associated lipocalin (NGAL) levels in mice were increased by cisplatin but decreased to normal ranges by maltol pretreatment (50 and 100 mg/kg) for ten days. Besides, maltol pretreatment decreased oxidative stress, lipid peroxidation and apoptosis in cisplatin-treated mice. The inhibitory action of maltol on inflammatory responses was achieved by reducing the expressions in NF-κB, IL-1β, iNOS, and TNF-α in the mice in vivo. Additionally, maltol restored the reduction of PI3K/Akt and mTOR levels by cisplatin through increasing AMPK expression in cisplatin-treated HEK293 cells. Maltol also suppressed the expression of Bax and caspase 3 by inhibiting the p53 activity in HEK293 cells. Overall, maltol may serve as a valuable potential drug to prevent cisplatin-induced nephrotoxicity, and the underlying molecular mechanisms of maltol action may involve intracellular AMPK/PI3K/Akt and p53 signaling pathways. |
| format |
article |
| author |
Xiao-jie Mi Jin-gang Hou Zi Wang Ye Han Shen Ren Jun-nan Hu Chen Chen Wei Li |
| author_facet |
Xiao-jie Mi Jin-gang Hou Zi Wang Ye Han Shen Ren Jun-nan Hu Chen Chen Wei Li |
| author_sort |
Xiao-jie Mi |
| title |
The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways |
| title_short |
The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways |
| title_full |
The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways |
| title_fullStr |
The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways |
| title_full_unstemmed |
The protective effects of maltol on cisplatin-induced nephrotoxicity through the AMPK-mediated PI3K/Akt and p53 signaling pathways |
| title_sort |
protective effects of maltol on cisplatin-induced nephrotoxicity through the ampk-mediated pi3k/akt and p53 signaling pathways |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/2ae4566f8538477387f5275278a4aaad |
| work_keys_str_mv |
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