Baldev N, Sriram R, Prabu P C, Kurian Gino A
School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
Vascular Biology Lab, SASTRA University, Thanjavur, Tamil Nadu, India.
Int Braz J Urol. 2015 Nov-Dec;41(6):1116-25. doi: 10.1590/S1677-5538.IBJU.2014.0585.
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.
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.
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.
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.
临床报告表明硫代硫酸钠（STS）是预防肾结石的一种有前景的药物。然而，其作用机制仍不清楚。在本研究中，我们研究了线粒体ATP敏感性钾通道（mitochondrial KATP channel）在STS介导的肾脏保护中的作用。
给Wistar大鼠饮用含0.4%乙二醇（EG）和1%氯化铵的水一周，随后仅饮用0.75% EG两周，诱导肾结石形成。治疗组分别单独给予STS、线粒体ATP敏感性钾通道开放剂和阻滞剂，或与STS联合给药两周。
接受STS治疗的动物肾组织结构正常，血清肌酐、尿素和碱性磷酸酶（ALP）活性接近正常，支持这一结果。给予动物二氮嗪（线粒体ATP敏感性钾通道开放剂）治疗也显示肾组织组织学正常，血清生化指标改善。然而，给予格列本脲（线粒体ATP敏感性钾通道阻滞剂）治疗的大鼠则出现相反的结果。STS与二氮嗪联合给药消除了二氮嗪单独给药所带来的肾脏保护作用，而对格列本脲治疗的大鼠具有保护作用，形成了线粒体调节的STS作用。
本研究证实，STS不仅通过螯合和抗氧化作用提供肾脏保护，还通过调节线粒体ATP敏感性钾通道来预防尿石症。
