Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from Ziziphus jujuba Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
- Authors
- Lee, Dahae; Kang, Kyo Bin; Hwang, Gwi Seo; Choi, You-Kyoung; Kim, Tae Kon; Kang, Ki Sung
- Issue Date
- Nov-2021
- Publisher
- MDPI
- Keywords
- Inflammation; LLC-PK1; Nephrotoxicity; Oxidative stress; Ziziphus jujuba Mill
- Citation
- Biomolecules, v.11, no.11
- Journal Title
- Biomolecules
- Volume
- 11
- Number
- 11
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82856
- DOI
- 10.3390/biom11111614
- ISSN
- 2218-273X
- Abstract
- 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 Ziziphus jujuba 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 Z. jujuba against cisplatin-induced kidney epithelial cell death. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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