Oleanolic acid is a molecule of current therapeutic interest. In the present study, oleanolic acid isolated from the cuticular epithelium of Viscum articulatum Burm. f. (Viscaceae) was investigated for its protective effects on gentamicin-induced renal damage in rats. Nephrotoxicity was induced in rats by intraperitoneal injection of gentamicin at a dose of 100 mg/kg/day for 8 days. The effect of Oleanolic acid administered orally at doses 40, 60 and 80 mg/kg/day was assessed biochemically by determination of albumin, urea and creatinine in serum and urine samples and also through histopathological examination of the kidneys. Oleanolic acid protected the rat kidneys from gentamicin-induced nephrotoxicity as evident from a decrease in the serum and urine levels of creatinine, albumin and urea. Oleanolic acid also protected the rat kidneys from histological alterations induced by gentamicin and also improved the glomerular filtration rate. Compared with an earlier report on intraperitoneal administration of oleanolic acid in paracetamol-induced nephrotoxicity in rats, the data show that orally administered oleanolic acid also exerted a nephroprotective effect even in the case of a nephrotoxicant such as gentamicin, which directly deteriorates the kidney function without prior metabolism.

The zinc disc implantation-induced urinary bladder calculi model in the rat is commonly used for preclinical evaluation of the antiurolithiatic activity of test compounds. Certain published reports state that relatively long durations for which zinc discs must be implanted in the bladders of rats. Hence, there is a need to refine this model. These investigations aimed to determine whether long-term studies using the zinc disc implantation model provide any additional data that affect the final outcomes of the study. In this study, we evaluated the effects of a well-known antiurolithiatic polyherbal drug, Cystone, for different treatment durations of 10, 20 and 48 days postimplantation. Our results indicate that even the shortest duration of 10 days is sufficient to reveal antiurolithiatic effects of a test drug. Hence, in the zinc disc implantation-induced urinary bladder calculi model, the study duration is proposed to be minimized so as to reduce the distress caused to the rats due to long-term exposure to the implant. Further, it is suggested that the growth of the bladder calculi can be monitored by taking X-ray radiographs of the bladder deposits to decide the time to terminate the study. Use of preformed calcium oxalate crystal instead of zinc discs, as suggested in earlier reports by others, may also be considered to avoid the sacrifice of rats at the end of the study. Formation of calculi (uroliths) in the kidneys, urinary bladder and ureters is a common urological disorder affecting approximately 12% of the world population with a considerable recurrence even after surgical removal.1 The preclinical evaluation of antiurolithiatic activity of drugs is carried out in the experimental models that represent the process of formation of kidney calculi and urinary bladder calculi. The in vitro models used for this purpose simulate the initial events in the urolith formation such as nucleation, supersaturation and crystal growth.2 However, such models do not encompass the activities of endogenous urolith inducers/inhibitors and biological processes that are actually involved in the stone formation in vivo. Hence, in the evaluation of the antiurolithiatic effect of test drugs, in vivo animal models are preferred.2,3 Rats are generally used as experimental animals for this purpose because there are considerable similarities in the structure and physiology of the urinary systems in humans and the rats. The models of urinary bladder stones include either chemical induction of stone formation or surgical implantation of foreign material like a zinc disc in the urinary bladder of rats that subsequently leads to deposition of an urolith around the implant. The formation of renal calculi can be chemically induced in the experimental animals by oral administration of ethylene glycol, ammonium chloride, vitamin D3, calcium gluconate, ammonium oxalate, gentamicin sulphate or L-hydroxyproline. 4 These chemicals either alter the biochemical processes leading to excessive oxalate formation or alter the composition of...