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Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice
In this study, the protective effects of pseudoginsengenin DQ (PDQ) on cisplatin (CDDP)-induced nephrotoxicity were assessed, with a primary investigation into the mechanisms involved. Our results showed that pretreatment with PDQ remarkably restored levels of blood urea nitrogen (BUN) and creatinin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278544/ https://www.ncbi.nlm.nih.gov/pubmed/30469321 http://dx.doi.org/10.3390/molecules23113038 |
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author | Qi, Zeng Li, Zhuo Li, Wei Liu, Yunhe Wang, Cuizhu Lin, Hongqiang Liu, Jinping Li, Pingya |
author_facet | Qi, Zeng Li, Zhuo Li, Wei Liu, Yunhe Wang, Cuizhu Lin, Hongqiang Liu, Jinping Li, Pingya |
author_sort | Qi, Zeng |
collection | PubMed |
description | In this study, the protective effects of pseudoginsengenin DQ (PDQ) on cisplatin (CDDP)-induced nephrotoxicity were assessed, with a primary investigation into the mechanisms involved. Our results showed that pretreatment with PDQ remarkably restored levels of blood urea nitrogen (BUN) and creatinine (CRE), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Meanwhile, PDQ decreased the CDDP-induced overexpression of heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1), TNF-α, nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in renal tissues. Hoechst 33258 and TdT-mediated dUTP nick-end labeling (TUNEL) staining showed that CDDP-induced renal tubular cell apoptosis was apparently inhibited by PDQ. Western blotting showed that PDQ reversed the CDDP-induced (1) downregulation of Sirtuin-1 (Sirt-1), nuclear-related factor 2 (Nrf2), and Bcl-2, and (2) upregulation of NF-κB, Nox-4, Bax, caspase-9, and caspase-3. In addition, PDQ enhanced the antitumor activity of cisplatin in Lewis lung cancer xenograft tumor model mice. In conclusion, we found that PDQ exerted a renal protective effect against CDDP-induced acute nephrotoxicity via Sirt1/NF-κB and the caspase signaling pathway without compromising the antitumor activity of CDDP, which provides a new potential strategy for the clinical treatment of cancer and presents a new medicinal application of PDQ. |
format | Online Article Text |
id | pubmed-6278544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62785442018-12-13 Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice Qi, Zeng Li, Zhuo Li, Wei Liu, Yunhe Wang, Cuizhu Lin, Hongqiang Liu, Jinping Li, Pingya Molecules Article In this study, the protective effects of pseudoginsengenin DQ (PDQ) on cisplatin (CDDP)-induced nephrotoxicity were assessed, with a primary investigation into the mechanisms involved. Our results showed that pretreatment with PDQ remarkably restored levels of blood urea nitrogen (BUN) and creatinine (CRE), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Meanwhile, PDQ decreased the CDDP-induced overexpression of heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1), TNF-α, nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in renal tissues. Hoechst 33258 and TdT-mediated dUTP nick-end labeling (TUNEL) staining showed that CDDP-induced renal tubular cell apoptosis was apparently inhibited by PDQ. Western blotting showed that PDQ reversed the CDDP-induced (1) downregulation of Sirtuin-1 (Sirt-1), nuclear-related factor 2 (Nrf2), and Bcl-2, and (2) upregulation of NF-κB, Nox-4, Bax, caspase-9, and caspase-3. In addition, PDQ enhanced the antitumor activity of cisplatin in Lewis lung cancer xenograft tumor model mice. In conclusion, we found that PDQ exerted a renal protective effect against CDDP-induced acute nephrotoxicity via Sirt1/NF-κB and the caspase signaling pathway without compromising the antitumor activity of CDDP, which provides a new potential strategy for the clinical treatment of cancer and presents a new medicinal application of PDQ. MDPI 2018-11-21 /pmc/articles/PMC6278544/ /pubmed/30469321 http://dx.doi.org/10.3390/molecules23113038 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Qi, Zeng Li, Zhuo Li, Wei Liu, Yunhe Wang, Cuizhu Lin, Hongqiang Liu, Jinping Li, Pingya Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice |
title | Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice |
title_full | Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice |
title_fullStr | Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice |
title_full_unstemmed | Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice |
title_short | Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice |
title_sort | pseudoginsengenin dq exhibits therapeutic effects in cisplatin-induced acute kidney injury via sirt1/nf-κb and caspase signaling pathway without compromising its antitumor activity in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278544/ https://www.ncbi.nlm.nih.gov/pubmed/30469321 http://dx.doi.org/10.3390/molecules23113038 |
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