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

Dahae Lee,Ki Sung Kang,You-Kyoung Choi,Kyo Bin Kang,Gwi Seo Hwang,Tae Kon Kim

doi:10.3390/biom11111614

Dahae Lee, Ki Sung Kang + Show 4 more

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https://doi.org/10.3390/biom11111614

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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.

Highlights

The kidneys perform a variety of pivotal functions, such as the control of fluids and solutes, metabolic waste excretion, endocrine function, and blood pressure control, as well as drug metabolism and excretion [1]
Kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase, 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 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from Z. jujuba against cisplatin-induced kidney epithelial cell death
Cisplatin is still widely prescribed in clinical practice, despite the high prevalence of cisplatin-induced nephrotoxicity (34.1%) [3]

Summary

Introduction

The kidneys perform a variety of pivotal functions, such as the control of fluids and solutes, metabolic waste excretion, endocrine function, and blood pressure control, as well as drug metabolism and excretion [1]. The kidneys are a major target for various drug-induced toxicities. Cisplatin-induced nephrotoxicity remains an important global medical problem [2]. Cisplatin is still widely prescribed in clinical practice, despite the high prevalence of cisplatin-induced nephrotoxicity (34.1%) [3]. Cisplatin induces nephrotoxicity and exerts toxic effects through one or more cellular mechanisms. In cisplatin-induced nephrotoxicity, elevated oxidative stress and decreased antioxidant enzymes can destroy cell organelle structures and interfere with cellular processes. Oxidative stress has been linked to apoptosis, inflammation, and mitochondrial

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