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Effects of Post Ischemia-Reperfusion Treatment with Trimetazidine on Renal Injury in Rats: Insights on Delayed Renal Fibrosis Progression

 Jin Ha Park  ;  Ji Hae Jun  ;  Jae-Kwang Shim  ;  Eun Jung Shin  ;  Eunah Shin  ;  Young-Lan Kwak 
 Oxidative Medicine and Cellular Longevity, Vol.2018 : 1072805, 2018 
Journal Title
 Oxidative Medicine and Cellular Longevity 
Issue Date
Even after recovery from acute kidney injury, glomeruli remain vulnerable to further injury by way of interstitial fibrosis. This study is aimed at elucidating the effects of post ischemia-reperfusion (I/R) treatment with trimetazidine on the progression to renal fibrosis as well as short- and intermediate-term aspects. Trimetazidine 3 mg/kg or 0.9% saline was given intraperitoneally once upon reperfusion or daily thereafter for 5 d or 8 w. Renal histologic changes and related signaling proteins were assessed. After 24 h, post I/R treatment with trimetazidine significantly reduced serum blood urea nitrogen and creatinine levels and tubular injury accompanied with upregulation of hypoxia-inducible factor- (HIF-) 1α, vascular endothelial growth factor (VEGF), and Bcl-2 expression. After 5 d, post I/R treatment with trimetazidine reduced renal tubular cell necrosis and apoptosis with upregulation of HIF-1α-VEGF and tissue inhibitors of metalloproteinase activities, attenuation of matrix metalloproteinase activities, and alteration of the ratio of Bax to Bcl-2 levels. After 8 w, however, post I/R treatment with trimetazidine did not modify the progression of renal fibrosis. In conclusion, post I/R treatment with trimetazidine allows ischemic kidneys to regain renal function and structure more rapidly compared to nontreated kidneys, but not enough to resolute renal fibrosis in long-term aspect.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실)
Yonsei Authors
곽영란(Kwak, Young Lan) ORCID logo https://orcid.org/0000-0002-2984-9927
박진하(Park, Jin Ha) ORCID logo https://orcid.org/0000-0002-1398-3304
심재광(Shim, Jae Kwang) ORCID logo https://orcid.org/0000-0001-9093-9692
전지혜(Jun, Ji Hae) ORCID logo https://orcid.org/0000-0002-8080-0715
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