Quercetin protects against radiocontrast medium toxicity in human renal proximal tubular cells.

Abstract

Radiocontrast media (RCM)-induced acute kidney injury (CI-AKI) is a major clinical problem whose pathophysiology is not well understood. Direct toxic effects on renal cells, possibly mediated by reactive oxygen species, have been postulated as contributing to CI-AKI. We investigated the effect of quercetin on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. Quercetin is the most widely studied flavonoid, and the most abundant flavonol present in foods. It has been suggested to have many health benefits, including angioprotective properties and anti-cancer effects. These beneficial effects have been attributed to its antioxidant properties and its ability to modulate cell signaling pathways. Incubation of HK-2 cells with 100 μM quercetin caused a decrease in cell viability and pre-treatment of HK-2 cells with 100 μM quercetin followed by incubation with 75 mgI/ml sodium diatrizoate for 2 hr caused a decrease in cell viability which was worse than in cells treated with diatrizoate alone. However, further incubation of the cells (for 22 hr) after removal of the diatrizoate and quercetin caused a recovery in cell viability in those cells previously treated with quercetin + diatrizoate and quercetin alone. Analysis of signaling molecules by Western blotting showed that in RCM-treated cells receiving initial pre-treatment with quercetin, followed by its removal, an increase in phosphorylation of Akt (Ser473), pSTAT3 (Tyr705), and FoxO3a (Thr32) as well as an induction of Pim-1 and decrease in PARP1 cleavage were observed. Quercetin may alleviate the longer-term toxic effects of RCM toxicity and its possible beneficial effects should be further investigated.

• Authors: Michele Andreucci, Teresa Faga, Antonio Pisani, Raffaele Serra, Domenico Russo, Giovambattista De Sarro, Ashour Michael
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 233 Issue 5 Pg. 4116-4125 (05 2018) ISSN: 1097-4652 [Electronic] United States
• PMID: 29044520 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antioxidants
• Contrast Media
• FOXO3 protein, human
• Forkhead Box Protein O3
• STAT3 Transcription Factor
• Diatrizoate
• Quercetin
• Proto-Oncogene Proteins c-akt

Topics

• Acute Kidney Injury (drug therapy, genetics, pathology)
• Antioxidants (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Contrast Media (pharmacology)
• Diatrizoate (pharmacology)
• Epithelial Cells (drug effects)
• Forkhead Box Protein O3 (genetics)
• Gene Expression (drug effects)
• Humans
• Kidney Tubules, Proximal (drug effects, pathology)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (genetics)
• Quercetin (pharmacology)
• STAT3 Transcription Factor (genetics)
• Signal Transduction (drug effects)