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Molecules 2018, 23(11), 3038; https://doi.org/10.3390/molecules23113038

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

1
School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China
2
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China
*
Author to whom correspondence should be addressed.
Received: 28 October 2018 / Revised: 19 November 2018 / Accepted: 19 November 2018 / Published: 21 November 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

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. View Full-Text
Keywords: pseudoginsengenin DQ; CDDP-induced acute kidney injury; Sirt1/NF-κB; caspase pseudoginsengenin DQ; CDDP-induced acute kidney injury; Sirt1/NF-κB; caspase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Qi, Z.; Li, Z.; Li, W.; Liu, Y.; Wang, C.; Lin, H.; Liu, J.; Li, P. 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. Molecules 2018, 23, 3038.

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