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Thiosulfate, an endogenous molecule

interesting results, where the protective effect shown by diazoxide treatment alone was negated by STS supplementation. On the other hand, STS supplementation to glibenclamide group showed preserved renal tissue architecture. This inverse relationship of STS is an evidence for its interaction with mito KATP Diazoxide binds to an ATP-sensitive K+ transport pathway in kidney mitochondria that affects volume, respiration, and membrane potential and may have a role in the prevention of mitochondrial ATP hydrolysis. Opening of this channel leads to mild uncoupling, blocks calcium entry into mitochondria and leading to renal protection . As both diazoxide and STS (mediated through H2S formation) binds to KATP channel in different sites, when diazoxide and STS are given concomitantly, long term or excessive uncoupling may be expected causing ATP hydrolysis and mPTP opening without impairing electron transport, leading to apoptosis. On the other hand, glibenclamide binds to different sulfonylurea subunit blocking potassium entry, thereby exaggerating the ROS production and destabilizing the membrane potential leading to apoptosis . When STS is given with glibenclamide, we predict that, H2S released from STS may bind to Kir6. 1 subunit of mito KATP channel, thereby reducing the binding efficiency of glibenclamide resulting its limited action of KATP channel, allowing STS to mediated its renal protection.

The protective mechanism induced by the opening of mito KATP is well-studied in cardiovascular diseases. Analogous to the heart system, renal protection by diazoxide may well be claimed due to i) Changes in the mitochondrial Ca2+ levels ii) Mitochondrial matrix swelling and changes in ATP synthesis iii) Changes in the ROS levels. Sodium thiosulfate is a known calcium chelating agent with antioxidant properties and can render electrons to complex IV upon its metabolism. Furthermore, several lines of the reports suggest that mitochondrial KATP channel opening may inhibit mitochondrial permeability transition through inhibiting calcium overload and thereby preserve mitochondrial functions.