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Article

Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death

by 1,†, 2,†, 2,* and 1,*
1
College of Korean Medicine, Gachon University, Seongnam 13120, Korea
2
Department of Biosystems and Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(6), 867; https://doi.org/10.3390/biom10060867
Received: 23 March 2020 / Revised: 22 May 2020 / Accepted: 3 June 2020 / Published: 5 June 2020
Iodixanol is a non-ionic iso-osmolar contrast agent, but it is a risk factor for kidney damage and increases morbidity and mortality. In this study, we investigated the effect of 9 sesquiterpenes isolated from mugwort (Artemisia argyi) in contrast agent-induced cytotoxicity in LLC-PK1 cells. Cells were exposed to nine sesquiterpene compounds for 2 h, followed by incubation with iodixanol for 3 h. Cell viability was assessed using the Ez-Cytox assay. The level of reactive oxygen species was measured using 2′,7′-dichlorodihydrofluorescein diacetate staining. Apoptotic cell death was detected using annexin V/PI staining. In addition, immunofluorescence staining and western blotting were performed using antibodies against proteins related to apoptosis, oxidative stress, and MAPK pathways. The most effective 3-epi-iso-seco-tanapartholide (compound 8) among the 9 sesquiterpene compounds protected LLC-PK1 cells from iodixanol-induced cytotoxicity, oxidative stress, and apoptotic cell death. Pretreatment with compound 8 reversed iodixanol-induced increases in the expression of JNK, ERK, p38, Bax, caspase-3, and caspase-9. It also reversed the iodixanol-induced decrease in Bcl-2 expression. Furthermore, pretreatment with compound 8 caused nuclear translocation of Nrf2 and upregulated HO-1 via the Nrf2 pathway in iodixanol-treated LLC-PK1 cells. Thus, we demonstrated here that compound 8 isolated from A. argyi has the potential to effectively prevent iodixanol-induced kidney epithelial cell death via the caspase-3/MAPK pathways and HO-1 via the Nrf2 pathway. View Full-Text
Keywords: apoptosis; contrast agent; cytotoxicity; iodixanol; oxidative stress apoptosis; contrast agent; cytotoxicity; iodixanol; oxidative stress
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MDPI and ACS Style

Lee, D.; Kim, K.O.; Lee, D.; Kang, K.S. Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death. Biomolecules 2020, 10, 867. https://doi.org/10.3390/biom10060867

AMA Style

Lee D, Kim KO, Lee D, Kang KS. Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death. Biomolecules. 2020; 10(6):867. https://doi.org/10.3390/biom10060867

Chicago/Turabian Style

Lee, Dahae, Kem O. Kim, Dongho Lee, and Ki S. Kang 2020. "Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death" Biomolecules 10, no. 6: 867. https://doi.org/10.3390/biom10060867

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