Nephroprotective and antilithiatic activities of Costus spicatus (Jacq.) Sw.: Ethnopharmacological investigation of a species from the Dourados region, Mato Grosso do Sul State, Brazil

Ethnopharmacological relevance: Costus spicatus (Jacq.) Sw., also known as "cana-do-brejo," is a species that is widely used in Brazilian traditional medicine for the treatment of kidney diseases. However, no studies have evaluated its nephroprotective and antilithiatic effects. Aim: To investigate nephroprotective and antilithiatic effects of C. spicatus in a preclinical model of acute kidney injury (AKI) and in vitro nephrolithiasis. Materials and methods: C. spicatus leaves were collected directly from the natural environment in the Dourados region, Mato Grosso do Sul State, Brazil. The ethanol-soluble fraction of C. spicatus (ESCS) was obtained by infusion. Phytochemical characterization was performed by liquid chromatography coupled to diode array detector and mass spectrometer (LC-DAD-MS). We assessed whether ESCS has acute or prolonged diuretic activity. The nephroprotective effects of ESCS were evaluated in a model of AKI that was induced by glycerol (10 ml/kg, intramuscularly) in Wistar rats. Different doses of ESCS (30, 100, and 300 mg/kg) were administered orally for 5 days before the induction of AKI. Urinary parameters were measured on days 1, 3, 5, and 7. Twenty-four hours after the last urine collection, blood samples were obtained for the biochemical analysis. Blood pressure levels, renal vascular reactivity, renal tissue redox status, and histopathological changes were measured. Antilithiatic effects were evaluated by in vitro crystallization. Calcium oxalate precipitation was induced by sodium oxalate in urine samples with ESCS at 0.05, 0.5, and 5 mg/ml. Results: From LC-DAD-MS analyses, flavonoids, saponins and other phenolic compounds were determined in the composition of ESCS. Significant reductions of the excretion of urinary total protein, creatinine, sodium, and potassium were observed in the AKI group, with significant histopathological damage (swelling, vacuolization, necrosis, and inflammatory infiltration) in the proximal convoluted tubule. Treatment with ESCS exerted a significant nephroprotective effect by increasing the urinary excretion of total protein, urea, creatinine, sodium, potassium, calcium, and chloride. All of the groups that were treated with ESCS exhibited a reduction of histopathological lesions and significant modulation of the tissue redox state. We also observed a concentrationdependent effect of ESCS on the crystallization of urinary crystals, with reductions of the size and proportion of monohydrated crystals. Conclusion: The data suggest that C. spicatus has nephroprotective and antilithiatic effects, suggesting possible effectiveness in its traditional use.