Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death

Cisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from <i>Zizip...

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Autores principales: Dahae Lee, Kyo Bin Kang, Gwi Seo Hwang, You-Kyoung Choi, Tae Kon Kim, Ki Sung Kang
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:b93a0c0258d649e8a14cc10417976a042021-11-25T16:52:48ZAntioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death10.3390/biom111116142218-273Xhttps://doaj.org/article/b93a0c0258d649e8a14cc10417976a042021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1614https://doaj.org/toc/2218-273XCisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from <i>Ziziphus jujuba</i> Mill. in LLC-PK1 cells following cisplatin-induced cytotoxicity. These cells were exposed to 3DC2ME for 2 h, followed by treatment with cisplatin for 24 h. The treated cells were subjected to cell viability analysis using the Ez-Cytox assay. Reactive oxygen species (ROS) were detected via 2′, 7′- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In addition, western blotting and fluorescent immunostaining were performed to evaluate protein expressions related to oxidative stress and inflammation pathways. Pretreatment with 3DC2ME protected LLC-PK1 cells from cisplatin-induced cytotoxicity and oxidative stress. In addition, pretreatment with 3DC2ME upregulated heme oxygenase 1 (HO-1) via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cisplatin-treated LLC-PK1 cells. Furthermore, the increase in the expressions of IκB kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in these cells was inhibited. These results provide basic scientific evidence for understanding the antioxidant and anti-inflammatory effects of 3DC2ME isolated from <i>Z. jujuba</i> against cisplatin-induced kidney epithelial cell death.Dahae LeeKyo Bin KangGwi Seo HwangYou-Kyoung ChoiTae Kon KimKi Sung KangMDPI AGarticle<i>Ziziphus jujuba</i> Mill.LLC-PK1nephrotoxicityoxidative stressinflammationMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1614, p 1614 (2021)
institution DOAJ
collection DOAJ
language EN
topic <i>Ziziphus jujuba</i> Mill.
LLC-PK1
nephrotoxicity
oxidative stress
inflammation
Microbiology
QR1-502
spellingShingle <i>Ziziphus jujuba</i> Mill.
LLC-PK1
nephrotoxicity
oxidative stress
inflammation
Microbiology
QR1-502
Dahae Lee
Kyo Bin Kang
Gwi Seo Hwang
You-Kyoung Choi
Tae Kon Kim
Ki Sung Kang
Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
description Cisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from <i>Ziziphus jujuba</i> Mill. in LLC-PK1 cells following cisplatin-induced cytotoxicity. These cells were exposed to 3DC2ME for 2 h, followed by treatment with cisplatin for 24 h. The treated cells were subjected to cell viability analysis using the Ez-Cytox assay. Reactive oxygen species (ROS) were detected via 2′, 7′- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In addition, western blotting and fluorescent immunostaining were performed to evaluate protein expressions related to oxidative stress and inflammation pathways. Pretreatment with 3DC2ME protected LLC-PK1 cells from cisplatin-induced cytotoxicity and oxidative stress. In addition, pretreatment with 3DC2ME upregulated heme oxygenase 1 (HO-1) via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cisplatin-treated LLC-PK1 cells. Furthermore, the increase in the expressions of IκB kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in these cells was inhibited. These results provide basic scientific evidence for understanding the antioxidant and anti-inflammatory effects of 3DC2ME isolated from <i>Z. jujuba</i> against cisplatin-induced kidney epithelial cell death.
format article
author Dahae Lee
Kyo Bin Kang
Gwi Seo Hwang
You-Kyoung Choi
Tae Kon Kim
Ki Sung Kang
author_facet Dahae Lee
Kyo Bin Kang
Gwi Seo Hwang
You-Kyoung Choi
Tae Kon Kim
Ki Sung Kang
author_sort Dahae Lee
title Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
title_short Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
title_full Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
title_fullStr Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
title_full_unstemmed Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
title_sort antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester isolated from <i>ziziphus jujuba</i> mill. against cisplatin-induced kidney epithelial cell death
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/b93a0c0258d649e8a14cc10417976a04
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