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.
Highlights
Urinary stone formation involves several factors, including the concentration of ions causing stone formation, urine pH, urinary flow rates, and urinary tract anatomy [1]
The mean MDA level of the ethylene glycol (EG) group was higher than the control group, while the mean MDA level of the quercetin group was significantly lower than the EG group (p = 0.001)
These results indicated that quercetin reduced the urinary oxalate levels, which were increased by EG administration
Summary
Urinary stone formation involves several factors, including the concentration of ions causing stone formation, urine pH, urinary flow rates, and urinary tract anatomy [1]. It is known that hyperoxaluria is an essential risk factor for the formation of these stones. The resultant increase in urinary oxalate concentration induces stone formation via calcium and oxalate ions to form CaOx crystals at physiological pH. It was demonstrated that the excess oxalate concentration damages kidney tubule cells via free oxygen radicals and increased lipid peroxidation and this process facilitates both the formation of CaOx crystals and their attachment to the kidney tubular epithelium [4,5]. Despite the improvements in renal stone treatment, the recurrence rates of 10% in one year, 35% in five years, and 50% in ten years were reported for calcium oxalate stones [6,7]
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