Fisetin Protects the Wistar Rats from the Oxidative and Inflammatory Damage Caused by Ethelene Glycol Induced Urolithiasis

Urolithiasis, commonly referred to as urinary stones, is the third most prevalent condition affecting the urinary system and affects 12% of people worldwide. In this investigation, we assessed the prospective flavonoid fisetin's anti-urolithiasis activity. Fisetin reduced the nucleation, aggregation, and crystallization of kidney stones in in vitro tests at dosages of 62.5, 125, 250, 500, and 1,000 ug/mL in a dose-dependent manner. Twenty-four male Wistar rats (n = 6) were induced with urolithiasis using ethylene glycol (0.75% v/v) with ammonium chloride (1% w/v) in drinking water for seven days. Except for the animals in the vehicle control and disease control groups, the remaining animals were supplemented with either Fisetin 15 mg/kg or 30 mg/kg body weight from days 7 to 21. On day 22, a urine evaluation showed that fisetin significantly increased the glycosaminoglycan (GAG) content, corrected urine pH, increased creatinine clearance, and increased urine volume. Additionally, fisetin decreased the levels of calcium, creatinine, uric acid, and N-acetyl glucouronidase (NAG) activity. Serum biochemical analysis revealed that fisetin reduced the excretion of creatinine, uric acid, and blood urea nitrogen (BUN). Further, fisetin reduced the content of total protein, calcium, oxalate, protein carbonyl content (PCC), malondialdehyde (MDA), tumor necrosis factor (TNF-α), interlukin-6 (IL-6), and increased the content of reduced glutathione (GSH), the activities of superoxide dismutase (SOD), and catalase (CAT). Histological findings also support our findings. Based on the above observations, fisetin can be a potential candidate for the treatment of urolithiasis.