With the increasing application of medical imaging contrast materials, contrast-induced nephropathy (CIN) has become the third major cause of iatrogenic renal insufficiency. CIN is defined as an absolute increase in serum creatinine levels of at least 0.50 mg/dl or an increase >25% of serum creatinine from baseline after exposure to contrast. In this study, the protective effects of salvianolic acid B (Sal B) were detected in human renal tubular epithelial cells (HK-2) exposed to iopromide. The results showed that different concentrations of Sal B counteract the loss of cell viability induced by iopromide, and reduce cell apoptosis, the reactive oxygen species (ROS) levels, and the levels of endoplasmic reticulum stress (ERS)–related and apoptosis-related proteins such as p-IRE-1α, p-eIF-2α/eIF-2α, p-JNK, CHOP, Bax/Bcl-2, and cleaved caspase-3. In addition, Sal B at a concentration of 100 μmol/L inhibited ERS and reduced cell damage to a similar extent as the ERS inhibitor 4-PBA. Importantly, treatment with Sal B could abolish the injury induced by ERS agonist tunicamycin, increasing cell viability and the mitochondrial membrane potential, as well as significantly reducing ROS levels and the expression of Bax/Bcl-2, cleaved-caspase-3, GRP78, p-eIF2α, p-JNK, and CHOP. These results suggested that the protective effect of Sal B against HK-2 cell injury induced by iopromide may be related to the inhibition of ERS.
Purpose In this study, we conducted to explore whether the protective effect of Salvianolic acid B (Sal B) on iopromide-induced human proximal tubular epithelial cells (HK-2 cells) injury is related to the inhibition of NLRP3 inflammasome (TRN: NL8582, registration date: 2020-05-01). Methods HK-2 cells were treated with several concentrations of iopromide or Sal B for 3 h, the cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. The levels of reactive oxygen species and the mitochondrial membrane potential were evaluated by DCFH-DA and rhodamine 123 staining, separately. The nucleus morphology of apoptotic cells was observed by DAPI staining. The expression levels of inflammation and apoptosis related proteins were detected by Western blot. In addition, after the introduction of TLR4 inhibitor (TAK-242) to pretreat the cells, the above indicators were detected. The free energy and the docking amino acid residues between Sal B and TLR4 or NLRP3 were analyzed. Results Sal B can stably bind to TLR4 or NLRP3, counteract the decrease of cell viability and MMP, the increase of ROS, the number of apoptotic cells, and the expression levels of the above proteins which induced by iopromide. The effect of TAK-242 is similar to that of 100 µmol/L Sal B. However, the pre-treatment group with TAK-242 and Sal B at the same time had no significant difference in cell viability and apoptosis rate compared with the pre-treatment group with TAK-242 or Sal B alone. Conclusions Sal B can reduce iopromide-induced HK-2 cells damage through inhibiting NLRP3 inflammasome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.