Background: Tribulus terrestris ( T. terrestris ) is traditionally used in the management of urinary disorders; however, evidence regarding its safety upon repeated administration and its antiurolithiatic efficacy remains limited. This study aimed to evaluate both the sub-acute toxicity and antiurolithiatic potential of the ethanol extract of T. terrestris (EETT) in experimental rats. Methods: Sub-acute toxicity was assessed in Wistar rats (n = 30; 5 males and 5 females per group) following 28-day repeated oral administration of EETT (500 and 1000 mg/kg). Antiurolithiatic activity was evaluated in an ethylene glycol/ammonium chloride-induced nephrolithiasis model (n = 36; 6 rats per group), where EETT (150, 300, and 450 mg/kg, intraperitoneally) was administered and compared with potassium citrate. Hematological, biochemical, and histopathological parameters were analyzed. Results: EETT exhibited no mortality or treatment-related toxicity, with no significant alterations in body weight, relative organ weights, hematological indices, or serum biochemical parameters. Histological examination confirmed normal tissue architecture in treated animals. In the nephrolithiasis model, EETT significantly ( P < 0.05) reduced elevated serum creatinine, urea, calcium, and potassium levels in a dose-dependent manner. Histopathological findings revealed decreased calcium oxalate crystal deposition and preservation of renal structure, particularly at higher doses, with effects comparable to potassium citrate. Conclusion: The findings demonstrate that EETT possesses a favorable safety profile alongside significant antiurolithiatic activity. This dual evidence supports its potential as a therapeutic candidate for nephrolithiasis and warrants further pharmacological and clinical investigation. Plain Language Summary: Kidney stones can cause severe pain and may affect long-term kidney health. Many people use herbal remedies such as Tribulus terrestris , but clear scientific evidence about its safety and effectiveness is still limited. In this study, we tested an ethanol extract of this plant in rats to evaluate both safety and its ability to reduce kidney stone formation. Repeated use for 28 days did not produce harmful effects at the tested doses. In addition, the extract reduced stone formation and helped maintain normal kidney structure and function. These findings suggest that Tribulus terrestris may be a potential candidate option for supporting kidney health. However, further studies in humans are required before it can be recommended for clinical use. Keywords: Tribulus terrestris , sub-acute toxicity, nephrolithiasis, renal protection, rats
Al-Mohamadi et al. (Fri,) studied this question.