The relationship between Tacrolimus-induced nephrotoxicity and Endothelin 1 on renal ischemic reperfusion injury model in spontaneously hypertensive rats
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概要
- 論文の詳細を見る
Objective : With regard to the mechanism of tacrolimus (Tac)-induced nephrotoxicity in a rat model of renal ischemic reperfusion injury, we hypothesized that examining the phenomenon and its response to Endothelin 1 may lead to improved prognosis in transplanted kidneys in humans. Materials and Method : Two experiments were conducted. Both experiments used 10-week-old male spontaneously hypertensive rats (SHR). Tacrolimus was administered (dosage 1 mg/kg or 2 mg/kg) daily for 2 weeks. In experiment 1, the SHR were divided into a nephrectomy group and a non-nephrectomy group. In experiment 2, the SHR were divided into an ischemic group and a non-ischemic group. The hematobio-chemical and pathological indices and the cytokines of these model rats were studied. Results : In experiment 1, the nephrectomy group showed significantly decreased creatinine clearance (CCr) levels, depending upon the Tac dosage. Histologically, severity of vacuolized deformity of the renal tubule varied with the Tac dosage. In experiment 2, the renal function in the ischemic group showed prompt improvement, using the BUN, Cr, and CCr levels as indices. Administering Tac to SHR with impaired reperfusion due to ischemia resulted in increased nephrotoxicity. Examination of the cytokines revealed that, although the expression of Endothelin 1 was induced by impaired reperfusion after ischemia, the expression of the endothelin-A receptor was suppressed. Discussion : Nephrotoxicity was markedly more severe in the rats with renal dysfunction than in the rats with normal renal function that had received the same dosage of Tac. Nephrotoxicity was potentiated by renal ischemic reperfusion injury, which suggests that Endothelin 1 was involved.
- 近畿大学の論文
著者
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Kurita Takashi
Department of Cardiovascular Medicine, National Cardiovascular Center
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MATSUURA Takeshi
Department of Urology, Kinki University School of Medicine
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Matsuura Takeshi
Department Of Urology Kinki University School Of Medicine
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Matsuura Takeshi
Department Of Applied Chemistry Faculty Of Science And Engineering Kinki University
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Nose Kazuhiro
Department of Urology, Kinki University School of Medicine
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Kurita Takashi
Department Of Cardiovascular Medicine National Cerebral And Cardiovascular Research Center
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Nose Kazuhiro
Department Of Urology Kinki University Sakai Hospital
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Nose Kazuhiro
Department Of Urology Kinki University School Of Medicine
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Kurita Takashi
Department Of Cardiovascular Dynamics National Cerebral And Cardiovascular Center Research Institute
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Kurita Takashi
Department of Urology, Kinki University School of Medicine
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