Influence of the ATP-sensitive potassium channel blocker glibenclamide on the nephroprotective effect of polydatin in cisplatin-induced acute kidney injury

Relevance. Acute kidney injury is a serious pathological process that often develops during treatment with cisplatin. The ability of the phytoalexin polydatin to reduce the negative impact of cisplatin on kidney function has previously been demonstrated. However, the mechanisms by which polydatin exerts its nephroprotective potential have not been fully elucidated.
Objective. To investigate the effect of the ATP-sensitive potassium channel blocker glibenclamide on the implementation of the nephroprotective effect of polydatin in modeling cisplatin-induced acute kidney injury.
Materials and methods. The study was conducted on 50 white laboratory male Wistar rats weighing 250-300g, which were divided into 5 groups (n = 10). Modeling of acute kidney injury was carried out by intraperitoneal administration of cisplatin at a dose of 5 mg/kg on the 1st and 8th days of the experiment. For the purpose of nephroprotection, polydatin was administered intragastrically daily at a dose of 12 mg/kg. To block ATP-sensitive potassium channels, glibenclamide was used intragastrically at a dose of 5 mg/kg 30 minutes before the administration of polydatin. 14 days after the first administration of cisplatin, laboratory and instrumental indicators of renal function were assessed.
Results. Adequate functioning of ATP-sensitive potassium channels plays a key role in the nephroprotective properties of polydatin in a model of cisplatin-induced acute kidney injury. Administration of glibenclamide to block ATP-sensitive potassium channels, combined with polydatin, was associated with a significant decrease in the protective potential of the latter: increased azotemia, deterioration of the glomerular filtration rate and fractional sodium excretion, and decreased renal microcirculation. Against the background of a decrease in the microcirculation index, the level of proteinuria also increased.
Conclusions. ATP-sensitive potassium channels have a significant influence on the implementation of the nephroprotective potential of polydatin in the modeling of cisplatin-induced acute kidney injury.

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