ABSTRACT
Purpose: Sodium thiosulfate (STS) is clinically reported to be a promising drug in preventing nephrolithiasis. However, its mechanism of action remains unclear. In the present study, we investigated the role of mitochondrial KATP channel in the renal protection mediated by STS. Materials and Methods: Nephrolithiasis was induced in Wistar rats by administrating 0.4% ethylene glycol (EG) along with 1% ammonium chloride for one week in drinking water followed by only 0.75% EG for two weeks. Treatment groups received STS, mitochondrial KATP channel opener and closer exclusively or in combination with STS for two weeks. Results: Animals treated with STS showed normal renal tissue architecture, supported by near normal serum creatinine, urea and ALP activity. Diazoxide (mitochondria KATP channel opening) treatment to the animal also showed normal renal tissue histology and improved serum chemistry. However, an opposite result was shown by glibenclamide (mitochondria KATP channel closer) treated rats. STS administered along with diazoxide negated the renal protection rendered by diazoxide alone, while it imparted protection to the glibenclamide treated rats, formulating a mitochondria modulated STS action. Conclusion: The present study confirmed that STS render renal protection not only through chelation and antioxidant effect but also by modulating the mitochondrial KATP channel for preventing urolithiasis.
Subject(s)
Animals , Male , Antioxidants/pharmacokinetics , Chelating Agents/pharmacology , Ethylene Glycol , Nephrolithiasis/prevention & control , Potassium Channels/pharmacology , Thiosulfates/pharmacology , Antioxidants/therapeutic use , Calcium Oxalate/metabolism , Chelating Agents/therapeutic use , Disease Models, Animal , Electrophoresis, Agar Gel , Kidney/drug effects , Kidney/pathology , Lipid Peroxidation/drug effects , Nephrolithiasis/pathology , Potassium Channels/therapeutic use , Random Allocation , Rats, Wistar , Reproducibility of Results , Treatment Outcome , Thiosulfates/therapeutic useABSTRACT
Con el propósito de facilitar la orientación y el estudio de los pacientes con hematuria macroscópica recurrente o microscópica persistente, dolor abdominal recurrente, disuria, infección urinaria recurrente o litiasis nefrourológica en las que puede estar involucrada la hipercalciuria idiopática, se hace esta presentación de forma sencilla, para que pueda ser empleada por el médico de atención primaria. La hipercalciuria idiopática es tan frecuente que afecta aproximadamente al 10 por ciento de la población y ante sus síntomas que pueden ser muy variados, hay que pensar en esta alteración metabólica hereditaria que es la causa más frecuente de litiasis renal cálcica. En ocasiones con una orientación adecuada y pocos o ningún medicamento se puede evitar que los pacientes desarrollen una litiasis nefrourológica o que la enfermedad litiásica progrese, y a la vez, impedir que estos pacientes, niños principalmente, sean sometidos a investigaciones cruentas...
In order to make possible the orientation and the study of patients presenting with recurrent macroscopic hematuria or persistent microscopic hematuria, recurrent abdominal pain, dysuria, recurrent urinary infection or nephrourologic lithiasis where a idiopathic hypercalciuria could be involved, we make this simple presentation that primary care physician could be used. Idiopathic hypercalciuria is so frequent that involves approximately to 10 percent`of population and in face of its symptoms that could be varied, we must to consider this hereditary metabolic alteration as the more frequent cause of calcium renal lithiasis. Some times with an appropriate orientation and a few or none drug it is possible to avoid that patient develop a nephrourologic lithiasis or that the lithiasis disease be progressive, and at the same time, to prevent that these patients, mainly the children underwent difficult researches...
Subject(s)
Humans , Child , Primary Health Care/methods , Hematuria/complications , Hematuria/diagnosis , Hypercalciuria/diagnosis , Hypercalciuria/epidemiology , Nephrolithiasis/prevention & controlABSTRACT
Esta obra ayuda de manera escueta, la patología renal y sus complicaciones, como por ejemplo: Cálculos renales, coólicos, diagnostico y tratamiento
Subject(s)
Male , Female , Humans , Nephrolithiasis/diagnosis , Nephrolithiasis/prevention & controlABSTRACT
Accumulated evidence from experiments conducted in vitro and in vivo favors a beneficial effect of the aqueous extract of Herniaria hirsuta in the preventionand cure of urolithiasis. In the current study, we attempted an initial fractionation of the methanol extract of the plant bio-guided by in vitro and in vivocrystallization assays to determine the nature of compound responsible for the beneficial effect of the plant. A ground plant sample was sequentiallysubmitted to ether and methanol extraction by soxhlet apparatus. Methanolic part was further purified by silica gel chromatography using a series of organicsolvents with different increasing polarity. The fractions were then assayed on calcium oxalate crystallization in vitro and in vivo models. In the whole humanurine, only the fraction eluted with ethanol/water was associated to formation of smaller crystals composed of calcium oxalate dihydrate, similarly to theaqueous extract. When tested at 5 mg/day, it reduced significantly crystal deposition in lithiasic rats. Preliminary identification of plant compound found inthat fraction showed the presence of saponins. We conclude that saponins may be responsible for the beneficial effect of Herniaria hirsuta in the treatmentof kidney stones.
A evidência acumulada por resultados de experimentos conduzidos in vitro e in vivo é favorável a uma ação benéfica do extrato aquoso da Herniaria hirsutana prevenção e cura da urolitíase. No presente estudo, nós nos propusemos a fazer um fracionamento inicial do extrato metanólico da planta,biologicamente guiado por ensaios de cristalização in vivo e in vitro, na tentativa de determinar a natureza do composto responsável pelo efeito benéficoda planta. A planta moída foi submetida seqüencialmente à extração por éter e metanol pelo equipamento "soxhlet". A porção metanólica foi adicionalmentepurificada por cromatografia em gel de sílica empregando uma série de solventes orgânicos de polaridade crescente. As frações foram então testadas emmodelos de cristalização de oxalato de cálcio in vivo e in vitro . Nos testes com urina humana total, somente a fração eluída com etanol/água esteveassociada a cristais menores, compostos de oxalato de cálcio di-hidratado, em similaridade com o extrato aquoso. Quando testada na dose de 5mg/dia,uma redução significativa na deposição de cristais foi observada em ratos litiásicos. Uma identificação preliminar dos compostos contidos naquela fraçãorevelou a presença de saponinas. Nós concluímos que saponinas podem ser responsáveis pelos efeitos benéficos da Herniaria hirsuta no tratamento decálculos renais.