Background Grape seed extract (GSE) has demonstrated various pharmacological actions. Urolithiasis is the occurrence of calculus in the renal system. The present study evaluated the anti-urolithic effect of GSE on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Materials and Methods Rats were assigned into six groups; Normal control and Normal + GSE, in which rats received standard drinking water and GSE orally daily, respectively; Urolithiatic animals received EG with AC in drinking water for 28 days; Urolithiatic animals + GSE, in which rats were administered EG with AC in drinking water and GSE 100 and 200 mg/kg orally; and Urolithiatic + cystone, where rats received EG with AC in drinking water and 750 g/kg of cystone as a standard drug orally. Results Urolithiatic animals showed a significant decrease in excreted magnesium and citrate and antioxidant enzymes, whereas they exhibited amplified oxalate crystal numbers, urinary excreted calcium, phosphate, oxalate ions, uric acid, intensified renal function parameters, lipid peroxidation, and inflammatory mediators. Management with GSE and cystone significantly augmented urolithiasis inhibitors (excreted magnesium and citrate) and amplified the antioxidant enzymes’ activities. GSE reduced oxalate crystal numbers and urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid excretion, lessened renal function parameters, and declined lipid peroxidation and the inflammatory mediators. Conclusion GSE could protect against EG-induced renal stones as evidenced by mitigated kidney dysfunction, histological alterations, and oxalate crystal formation. This action may be related to the antioxidant as well as anti-inflammatory activities of the extracts.
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