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Drug
Enzyme
Compound
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Target Concepts:
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Query: EC:3.4.22.62 (
caspase-9
)
7,507
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Anti-Apoptotic and Antioxidant Effects of 3-
Epi-
Iso
-Seco
-Tanapartholide Isolated from
Artemisia Argyi
Against Iodixanol-Induced Kidney Epithelial Cell Death. 3251 90