Sub-Acute Toxicity Evaluation and Antiurolithiatic Activity of Tribulus terrestris Ethanol Extract in Rats

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.

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.

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.

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.