Attenuation of Skeletal Muscle and Renal Injury to the Lower Limb following Ischemia-Reperfusion Using mPTP Inhibitor NIM-811

作者：Garbaisz David^*; Turoczi Zsolt; Aranyi Peter; Fulop Andras; Rosero Oliver; Hermesz Edit; Ferencz Agnes; Lotz Gabor; Harsanyi Laszlo; Szijarto Attila

来源：PLos One, 2014, 9(6): e101067.

DOI：10.1371/journal.pone.0101067

Introduction: Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP). %26lt;br%26gt;Objectives: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. %26lt;br%26gt;Materials and methods: Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-alpha and IL-6 levels were measured. %26lt;br%26gt;Results: Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p%26lt;0.001; CK: p%26lt; 0.001; K+: p = 0.017). Muscle mitochondrial viability proved to be significantly higher (p = 0.001) and renal function parameters were significantly better (creatinine: p = 0.016; FENa: p%26lt;0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-alpha and IL-6 levels were significantly lower (TNF-alpha: p = 0.003, IL-6: p = 0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p = 0.014; p%26lt;0.001) in the NIM-IR group than in the IR group. %26lt;br%26gt;Conclusion: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury.

• 出版日期2014-6-26