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.

Quercetin promotes in vitro maturation of oocytes from humans and aged mice

“…To reduce age-related oxidative stress and potentially relieve ROS-induced damage, biologists and medical scientists have explored the use of many antioxidant supplementations, including for example resveratrol, growth hormone, melatonin, rapamycin, and coenzyme Q10 [13][14][15][16][17] . Quercetin (3, 3′, 4′, 5, 7-pentahydroxylflavone) is a flavonoid natural product compound found in plants such as berries, broccoli, apples, and onions 18 . Previous studies have reported that quercetin can prevent mitochondrial dysfunction by removing oxidation products, scavenging free radicals, and stimulating antioxidant enzymes 19 .…”

Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation

“…In the case of kidney disease, it has been reported that quercetin can protect radiation‐induced DNA damage and apoptosis in kidney of rats (Ozyurt et al, ) and alleviate acute endotoxemic kidney injury in mice via suppression of inflammation and up‐regulation of antioxidants and SIRT1 (Khajevand‐Khazaei et al, ). Furthermore, quercetin also showed protective effects on Hgcl 2 ‐ and cisplatin‐induced nephrotoxicity in vivo (Sanchez‐Gonzalez et al, ; Shin et al, ) and protects against radiocontrast medium toxicity in human renal proximal tubular cells in vitro (Andreucci et al, ). Notably, a recent study demonstrated that quercetin ameliorates kidney injury and fibrosis by modulating M1/M2 macrophage polarization (Lu et al, ), which provides evidence to reveal that quercetin improves kidney inflammation and injury may be related to regulation of macrophage activity.…”

Transit and Metabolic Pathways of Quercetin in Tubular Cells: Involvement of Its Antioxidant Properties in the Kidney

“…Thus, in a study with HK-2 cells, i.e., human proximal tubular cells, it was suggested that quercetin is metabolized within a few minutes or even seconds of being incorporated into the culture medium. These cells contain UGT enzymes so it is possible that quercetin is transformed when cells are incubated with the flavonoid [72]. Furthermore, it has been suggested that these metabolites could be involved in the induction of antioxidant defense mechanisms through antioxidant response elements (AREs), inducing the expression of antioxidant enzymes [72].…”

“…These cells contain UGT enzymes so it is possible that quercetin is transformed when cells are incubated with the flavonoid [72]. Furthermore, it has been suggested that these metabolites could be involved in the induction of antioxidant defense mechanisms through antioxidant response elements (AREs), inducing the expression of antioxidant enzymes [72]. Another in vitro study revealed that taxifolin has renoprotective effects [63].…”