Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death
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 (<i>Artemisia argyi</i>) in contrast agent-induced cytotoxicity in LLC...
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MDPI AG
2020-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/6/867 |
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| author | Dahae Lee Kem Ok Kim Dongho Lee Ki Sung Kang |
| author_facet | Dahae Lee Kem Ok Kim Dongho Lee Ki Sung Kang |
| author_sort | Dahae Lee |
| collection | DOAJ |
| description | 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 (<i>Artemisia argyi</i>) 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-<i>epi</i>-iso-<i>seco</i>-tanapartholide (compound <b>8</b>) among the 9 sesquiterpene compounds protected LLC-PK1 cells from iodixanol-induced cytotoxicity, oxidative stress, and apoptotic cell death. Pretreatment with compound <b>8</b> 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 <b>8</b> 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 <b>8</b> isolated from <i>A. argyi</i> 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. |
| first_indexed | 2024-03-10T19:20:39Z |
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| id | doaj.art-374050eb9f7e489d97edb14e3c0d95ae |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T19:20:39Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-374050eb9f7e489d97edb14e3c0d95ae2023-11-20T02:59:44ZengMDPI AGBiomolecules2218-273X2020-06-0110686710.3390/biom10060867Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell DeathDahae Lee0Kem Ok Kim1Dongho Lee2Ki Sung Kang3College of Korean Medicine, Gachon University, Seongnam 13120, KoreaDepartment of Biosystems and Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, KoreaDepartment of Biosystems and Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaIodixanol 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 (<i>Artemisia argyi</i>) 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-<i>epi</i>-iso-<i>seco</i>-tanapartholide (compound <b>8</b>) among the 9 sesquiterpene compounds protected LLC-PK1 cells from iodixanol-induced cytotoxicity, oxidative stress, and apoptotic cell death. Pretreatment with compound <b>8</b> 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 <b>8</b> 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 <b>8</b> isolated from <i>A. argyi</i> 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.https://www.mdpi.com/2218-273X/10/6/867apoptosiscontrast agentcytotoxicityiodixanoloxidative stress |
| spellingShingle | Dahae Lee Kem Ok Kim Dongho Lee Ki Sung Kang Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death Biomolecules apoptosis contrast agent cytotoxicity iodixanol oxidative stress |
| title | Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death |
| title_full | Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death |
| title_fullStr | Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death |
| title_full_unstemmed | Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death |
| title_short | Anti-Apoptotic and Antioxidant Effects of 3-<i>Epi</i>-Iso-<i>Seco</i>-Tanapartholide Isolated from <i>Artemisia argyi</i> against Iodixanol-Induced Kidney Epithelial Cell Death |
| title_sort | anti apoptotic and antioxidant effects of 3 i epi i iso i seco i tanapartholide isolated from i artemisia argyi i against iodixanol induced kidney epithelial cell death |
| topic | apoptosis contrast agent cytotoxicity iodixanol oxidative stress |
| url | https://www.mdpi.com/2218-273X/10/6/867 |
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