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Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells.

Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells.
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Hwang BS, Lee D, Choi P, Kim KS, Choi SJ, Song BG, Kim T, Song JH, Kang KS, Ham J,


Hwang BS, Lee D, Choi P, Kim KS, Choi SJ, Song BG, Kim T, Song JH, Kang KS, Ham J, (click to view)

Hwang BS, Lee D, Choi P, Kim KS, Choi SJ, Song BG, Kim T, Song JH, Kang KS, Ham J,

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International journal of molecular sciences 2018 03 2219(4) pii 10.3390/ijms19040948

Abstract

Although cisplatin is the standard platinum-based anticancer drug used to treat various solid tumors, it can cause damage in normal kidney cells. Protective strategies against cisplatin-induced nephrotoxicity are, therefore, clinically important and urgently required. To address this challenge, we investigated the renoprotective effects of, a ball-shaped wood-rotting fungus. Chemical investigation of the active fraction from the methanol extract ofresulted in the isolation and identification of the renoprotective compounds, hypoxylonol C and F, which ameliorated cisplatin-induced nephrotoxicity to approximately 80% of the control value at 5 μM. The mechanism of this effect was further investigated using hypoxylonol F, which showed a protective effect at the lowest concentration. Upregulated phosphorylation of p38, extracellular signal-regulated kinases, and c-Jun-terminal kinases following cisplatin treatment were markedly decreased after pre-treatment with hypoxylonol F. In addition, the protein expression level of cleaved caspase-3 was significantly reduced after co-treatment with hypoxylonol F. These results show that blocking the mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of hypoxylonol F isolated fromfruiting bodies.

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