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Int. J. Mol. Sci. 2018, 19(1), 174; https://doi.org/10.3390/ijms19010174

Chemical Characterization of a Renoprotective Metabolite from Termite-Associated Streptomyces sp. RB1 against Cisplatin-Induced Cytotoxicity

1,†
,
2,†
,
3,* and 1,*
1
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
2
College of Korean Medicine, Gachon University, Seongnam 13120, Korea
3
Department of Food and Nutrition, Gachon University, Seongnam 13120, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 4 November 2017 / Revised: 2 January 2018 / Accepted: 3 January 2018 / Published: 7 January 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Platinum-based anticancer drug therapies can cause renal damage and apoptotic kidney cell damage. The development of reno- and kidney-protective molecules is therefore urgently required. To address this challenge, we explored secondary metabolites of termite-associated Streptomyces sp. RB1 isolated from the cuticle of the South African termite, Macrotermes natalensis for their renoprotective ability using bioassay-guided fractionation and LLC-PK1 cells. Chemical investigation of the MeOH extract of Streptomyces sp. RB1 resulted in the isolation and identification of a renoprotective metabolite, 1-O-(2-aminobenzoyl)-α-l-rhamnopyranoside (ABR) (1) from the active fraction, which ameliorated cisplatin-induced cytotoxicity to 80% of the control value at 25 μM. Upregulated phosphorylation of c-Jun N-terminal kinases (JNK) and p38 following cisplatin treatment was markedly decreased after pre-treatment of cells with ABR. In addition, levels of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after pre-treatment with ABR. These findings provide experimental evidence that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of ABR, which may inspire the development of novel therapeutic substances to prevent anticancer drug-induced nephrotoxicity. View Full-Text
Keywords: Streptomyces sp. RB1; 1-O-(2-aminobenzoyl)-α-l-rhamnopyranoside; LLC-PK1 cells; renoprotective effect; nephrotoxicity; MAPKs Streptomyces sp. RB1; 1-O-(2-aminobenzoyl)-α-l-rhamnopyranoside; LLC-PK1 cells; renoprotective effect; nephrotoxicity; MAPKs
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Lee, D.; Kang, K.S.; Lee, H.-J.; Kim, K.H. Chemical Characterization of a Renoprotective Metabolite from Termite-Associated Streptomyces sp. RB1 against Cisplatin-Induced Cytotoxicity. Int. J. Mol. Sci. 2018, 19, 174.

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