Postconditioning with cyclosporine a reduces early renal dysfunction by inhibiting mitochondrial permeability transition

Transplantation
Sandrine LemoineLaurent Juillard

Abstract

Ischemia-reperfusion (IR) injury leads to mitochondrial permeability transition pore opening, which contributes to cell death. The aim of this study is to determine whether ischemic or pharmacological postconditioning with cyclosporine A (CsA) might protect the kidney from lethal reperfusion injury. Male mice underwent a unilateral (right) nephrectomy followed by 30 minutes of contralateral (left) clamping of the renal artery. We studied 4 groups at 20 minutes and 24 hours of reperfusion: a sham group (n = 4), an ischemic group (n = 6), CsA-postconditioned group (postcond-CsA, injection of 3 mg/kg of CsA 5 minutes before the end of ischemia, (n = 6), and an ischemic postconditioning (IPC) group (n = 6), consisting of 3 cycles of 30 seconds of renal ischemia with 30 seconds intervening reperfusion. After 24 hours of reperfusion, we measured plasma creatinine, urea, and histological kidney injury. The kidney mitochondria were isolated to assess the mitochondria calcium retention capacity and oxidative phosphorylation. At 24 hours after reperfusion, serum creatinine decreased in postcond-CsA and IPC compared to ischemic group. The histological score was also significantly improved with postcond-CsA and IPC. At 20 minutes and 24 ho...Continue Reading

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Citations

Dec 30, 2015·Fundamental & Clinical Pharmacology·Laurent MonassierAtul Pathak
Apr 18, 2016·Seminars in Nephrology·Shrikant R MulayHans-Joachim Anders
Apr 14, 2017·Acta Cirúrgica Brasileira·Sylvio Valença de LemosPedro Thadeu Galvão Vianna
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Dec 16, 2020·ACS Biomaterials Science & Engineering·Xinlong ZangXuehong Chen

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