RESUMO
The study aimed to investigate the potential antiurolithic effects of extracts, fractions, and betulinic acid (BA) from Citharexylum mirianthum. In vitro analysis involved precipitating calcium oxalate (CaOx) crystals in urine. For in vivo studies, rats were divided into four groups: naive; vehicle; potassium citrate (KC); and BA. Urolithiasis was induced using ethylene glycol and ammonium chloride. After seven days, urine, blood, and kidney tissues were evaluated. The results showed that methanolic extract, hexane, dichloromethane, and ethyl acetate fractions, as well as BA, reduced CaOx crystal formation. In vivo, the vehicle-treated group exhibited reduced urinary volume and Na+ excretion, while the BA-treated group showed restored urinary volume and Na+ excretion similar to the naive group. BA also significantly reduced urinary monohydrate and dihydrate crystal formation, comparable to the KC group. Other urinary parameters remained unchanged, but plasma analysis revealed decreased Na+, K+, and Ca2+ in the KC group. Renal tissue analysis indicated reduced lipid hydroperoxides and increased reduced glutathione in all urolithiasis groups, with unchanged nitrite levels. BA treatment also improved renal corpuscle morphology. Overall, our findings demonstrate that treatment with BA effectively prevented kidney damage induced by EG+AC ingestion, thereby improving renal function in the urolithiasis model.
RESUMO
This study aimed to assess the ability of rosmarinic acid (RA) to prevent kidney stone formation in an ethylene glycol and ammonium chloride (EG/AC) model. There was an increase in diuresis in the normotensive (NTRs) and hypertensive rats (SHRs) treated with hydrochlorothiazide (HCTZ) and exposed to EG/AC, while RA restored urine volume in NTRs. The EG/AC groups exhibited lower urine pH and electrolyte imbalance; these parameters were not affected by any of the treatments. Both HCTZ+EG/AC and RA+EG/AC reduced calcium oxalate crystal formation in NTR and SHR urine. Kidney tissue analysis revealed alterations in oxidative stress and inflammation parameters in all EG/AC-receiving groups, with RA enhancing antioxidant defenses in SHRs. Additionally, crystals were found in the kidney histology of all EG/AC-exposed groups, with reduced Bowman's capsule areas in NTRs and SHRs. The NTR VEH+EG/AC group showed intense renal damage, while the others maintained their structures, where treatments with HCTZ and RA were fundamental for kidney protection in the NTRs. Docking analysis showed that RA exhibited good binding affinity with matrix metalloproteinase-9, phosphoethanolamine cytidylyltransferase, and human glycolate oxidase enzymes. The data disclosed herein underscore the importance of further research to understand the underlying mechanisms better and validate the potential of RA for clinical use.
RESUMO
BACKGROUND: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. METHODS: Wistar rats were used and the urine volume was noted for 8 h and further studied. RESULTS: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ââremained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization. CONCLUSIONS: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.