Prophylactic treatment with antioxidant nanoparticles attenuate ischemia/reperfusion injury in BALB/c mice
Se-Hee Yoon1, Won-Min Hwang1, Sung-Ro Yoon1, Sang-Eun Hong 2, Kuk Ro Yoon 2.
1Internal Medicine, Konyang University, College of Medicine, Daejeon , Korea; 2Chemistry , Hannam University , Daejeon, Korea
Aim: Ischemia/reperfusion injury is one of the important cause of delayed graft function, graft rejection and chronic graft dysfunction. Ceria nanoparticle (C NP) is known that exhibit free radical scavenger and catalytic activities. When zirconia attached to ceria nanoparticles, the ceria atom tend to remain Ce3+ and the efficacy as a free radical scavenger increase. We studied whether ceria and ceria-zirconia nanoparticles (CZ NPs) as an antioxidant are effective to protect ischemia/reperfusion injury in kidneys.
Method: CZ NPs were synthesized using a modified reverse micelle method. BALB/c mice were randomized into four groups: Group 1(control, normal saline pretreatment plus sham operation; n = 6), Group 2 (CZ NPs pretreatment plus sham operation; n = 6), Group 3 [normal saline pretreatment plus ischemia/reperfusion (I/R); n = 6] and Group 4 (CZ NPs pretreatment plus I/R; n = 6). Group 1 and Group 3 were administered 2ml/kg of normal saline intraperitoneally 4 hours before the I/R injury Group 2 and Group 4 received 10mg/kg (2ml/kg) of CZ NPs.
Results: After FITC-CZ NPs were administered intraperitoneally to BALB/c mice, we confirmed that FITC-CZ NPs successfully reached to both kidneys with confocal microscopy imaging. The levels of Plasma BUN and creatinine of Group 3 (I/R operation) were significantly increased when compared to Group 1 (control, sham operation). However, in Group 4 (CZ NPs + I/R operation), the plasma levels of BUN and creatinine were significantly decreased when compared to Group 3 (I/R operation). In Hematoxylin and Eosin staining for analyzing histologic changes there was no significant difference between Group1 and Group 2, but tubular dilatation, cellular casts, loss of tubular brush borders, vacuolar degeneration and tubular epithelial cell shedding were observed in Group 3. In Group 4, tubular damage was restored when compared to Group 3. To detect apoptotic changes in kidney cells, TUNEL assay was done. In Group 3, there was a significant number of positive cells in the TUNEL staining, whereas in Group 4, the number of TUNEL positive cells was significantly decreased.
Conclusion: Collectively, CZ NPs were successfully uptaken into kidney cells and effectively attenuated ischemia/reperfusion induced acute kidney injury in vivo, suggesting that could be a novel approach to control ischemia/reperfusion injury induced graft injury.
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