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
Calcium oxalate urolithiasis is one of the most common urinary tract diseases and is of high prevalence. The present study proposes to evaluate the antilithiatic property of hydrogen sulfide and its metabolites like thiosulfate & sulfate in an in vitro model.
The antilithiatic activity of sodium hydrogen sulfide (NaSH), sodium thiosulfate (Na2S2O3) and sodium sulfate (Na2SO4) on the kinetics of calcium oxalate crystal formation was investigated both in physiological buffer and in urine from normal and recurrent stone forming volunteers. The stones were characterized by optical and spectroscopic techniques.
The stones were characterized to be monoclinic, prismatic and bipyramidal habit which is of calcium monohydrate and dihydrate nature. The FTIR displayed fingerprint corresponding to calcium oxalate in the control while in NaSH treated, S=O vibrations were visible in the spectrum. The order of percentage inhibition was NaSH>Na2S2O3>Na2SO4.
Our study indicates that sodium hydrogen sulfide and its metabolite thiosulfate are inhibitors of calcium oxalate stone agglomeration which makes them unstable both in physiological buffer and in urine. This effect is attributed to pH changes and complexing of calcium by S2O32-and SO42- moiety produced by the test compounds.