Protective Effects of Quercetin on Oxidative Stress-Induced Tubular Epithelial Damage in the Experimental Rat Hyperoxaluria Model

Abstract

Background and Objectives: The most common kidney stones are calcium stones and calcium oxalate (CaOx) stones are the most common type of calcium stones. Hyperoxaluria is an essential risk factor for the formation of these stones. Quercetin is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects. The aim of this study was to investigate the protective effect of quercetin in hyperoxaluria-induced nephrolithiasis. Materials and Methods: Male Wistar-Albino rats weighing 250–300 g (n = 24) were randomized into three groups: Control (n = 8), ethylene glycol (EG) (n = 8), and EG + quercetin (n = 8). One percent EG-water solution was given to all rats except for the control group as drinking water for five weeks. Quercetin-water solution was given to the EG + quercetin group by oral gavage at a dose of 10 mg/kg/day. Malondialdehyde (MDA), catalase (CAT), urea, calcium, and oxalate levels were analyzed in blood and urine samples. Histopathological assessments and immunohistochemical analyses for oxidative stress and inflammation indicators p38 mitogen-activated protein kinase (p38-MAPK) and nuclear factor kappa B (NF-kB) were performed on renal tissues. Results: The MDA levels were significantly lower in the quercetin-treated group than in the EG-treated group (p = 0.001). Although CAT levels were higher in the quercetin-treated group than the EG-administered group, they were not significantly different between these groups. The expression of p38 MAPK was significantly less in the quercetin-treated group than the EG group (p < 0.004). There was no statistically significant difference between the quercetin and EG groups in terms of NF-kB expression. Conclusions: We conclude that hyperoxaluria activated the signaling pathways, which facilitate the oxidative processes leading to oxalate stone formation in the kidneys. Our findings indicated that quercetin reduced damage due to hyperoxaluria. These results imply that quercetin can be considered a therapeutic agent for decreasing oxalate stone formation, especially in patients with recurrent stones due to hyperoxaluria.

Mechanism of Xiezhuo Huayu Yiqi Tongluo Formula in the Treatment of Uric Acid Nephropathy Based on Network Pharmacology, Molecular Docking, and In Vivo Experiments

“…It has been reported that quercetin can inhibit renal inflammation and fibrosis in UUO and LPS mouse models by decreasing expressions of IL-18, IL-1 β , TNF- α , and fibrosis area in Masson staining and inhibiting collagen expression [ 20 ]. In addition, quercetin has a protective effect on renal tubular epithelial cell injury induced by oxidative stress in hyperoxaluria rats [ 21 ]. Therefore, we verified the binding ability of the key compounds to the five core genes through molecular docking simulation, and the docking results revealed that these compounds could stably bind to the active pocket of the core protein.…”

Perspective Chapter: Medicinal Plants for the Treatment of Nephrolithiasis

“…Many flavonoids such as quercitin, hyperoside, rutin, diosmin, and apigenin have been investigated for their probable potential to inhibit the formation of kidney stones. Table 1 summarizes the main findings regarding the anti-nephrolithiatic activity of flavonoids [12][13][14][15][16].…”

“…In vivo Reduced damage due to hyperoxaluria. Reduced oxalate stone formation [12] Quercetin and hyperoside…”

Editorial: Immunity and Inflammatory Response in Kidney Stone Disease

“…Inactivating NLRP3 may prevent oxalate damage by altering macrophage polarization. Antioxidant treatment of experimentally induced hyperoxaluria in rats also reduces the inflammatory responses and production of the inflammatory mediators (23,24). Indeed, inflammation in kidney stone disease can be the upstream (as a pathogenic factor) or downstream event (as a complication).…”

“…Inactivating NLRP3 may prevent oxalate damage by altering macrophage polarization. Antioxidant treatment of experimentally induced hyperoxaluria in rats also reduces the inflammatory responses and production of the inflammatory mediators ( 23 , 24 ).…”