E-selectin-targeted microbubbles combined with ultrasound improves renoprotective effects of methylprednisolone on cisplatin-induced acute kidney injury in rats
摘要
Our previous study showed that the functionalized E-selectin targeted MBs (TMB-E−selectin) may become a novel drug delivery vector for inflammatory diseases. Therefore, the purpose of this study was to investigate the effect of TMB-E−selectin and methylprednisolone (MP) co-administration combined with ultrasound (US) on cisplatin-induced acute kidney injury (AKI) in rats. After modeling with a single intraperitoneal injection of 10 mg/kg of cisplatin, the rats were intravenously administered with MP or TMB-E−selectin alone, or their mixtures. US was immediately applied for 10 min on bilateral kidneys in rats with TMB-E−selectin treatment. Results showed that 50 mg/kg MP alone and the mixture of 20 mg/kg MP and 500 µL/kg TMB-E−selectin combined with US significantly reduced the levels of BUN and Scr, renal injuries, and the expressions of E-selectin, IL-1α, TNF-α, and NF-κB in renal tissues, but these therapy effects were not significantly observed by 20 mg/kg MP alone. In conclusion, TMB-E−selectin combined with US can enhance the anti-inflammatory and renoprotective effects of the MP in rats with AKI then decrease systemic required dosage and improve the bioavailability of glucocorticoids, which mechanism mainly associates with local drug delivery mediated by US targeted microbubbles cavitation.