Dose-dependent nephroprotective effects of the synthetic leu-enkephalin analog dalargin in a rat model of renal ischemia-reperfusion injury

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Abstract
The objective was to investigate the nephroprotective effects of dalargin, a synthetic analog of leu-enkephalin, in a rat model of renal ischemia–reperfusion injury, and to evaluate its impact on the expression and phosphorylation of glycogen synthase kinase-3β (GSK-3β). Materials and methods . Acute kidney injury (AKI) was induced in Wistar rats by 60-minute warm renal ischemia combined with contralateral nephrectomy. Dalargin was administered intraperitoneally at doses of 1, 5, and 10 μg/kg. Serum creatinine and urea levels were measured. GSK-3β expression and phosphorylation were assessed by immunoblotting. Morphological changes in renal tissue were evaluated histologically. Results . Dalargin administration resulted in a dose-dependent attenuation of AKI severity, most pronounced at a dose of 10 μg/kg. This effect was associated with a statistically significant improvement in renal function parameters, increased levels of phosphorylated GSK-3β (pGSK-3β), and reduced histological signs of tubular necrosis. In the lowest-dose group (1 μg/kg), a trend toward worsened functional parameters was observed, possibly related to a survivor selection effect. Conclusion . The findings demonstrate a marked dose-dependent nephroprotective effect of dalargin in renal ischemia–reperfusion injury, associated with inhibition of GSK-3β activity. These results support further investigation of dalargin as a component of organ-protective strategies in critical care settings.

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