Attenuation of Skeletal Muscle and Renal Injury to the Lower Limb following Ischemia-Reperfusion Using mPTP Inhibitor NIM-811
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-reperfus...
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| Dokumentumtípus: | Cikk |
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2014
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| Sorozat: | PLOS ONE
9 No. 6 |
| Tárgyszavak: | |
| doi: | 10.1371/journal.pone.0101067 |
| mtmt: | 2704020 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/29351 |
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| 024 | 7 | |a 10.1371/journal.pone.0101067 |2 doi | |
| 024 | 7 | |a 2704020 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
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| 100 | 1 | |a Garbaisz Dávid | |
| 245 | 1 | 0 | |a Attenuation of Skeletal Muscle and Renal Injury to the Lower Limb following Ischemia-Reperfusion Using mPTP Inhibitor NIM-811 |h [elektronikus dokumentum] / |c Garbaisz Dávid |
| 260 | |c 2014 | ||
| 300 | |a 12 | ||
| 490 | 0 | |a PLOS ONE |v 9 No. 6 | |
| 520 | 3 | |a 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). OBJECTIVES: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811. 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 NIM-811 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. 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<0.001; CK: p<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<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<0.001) in the NIM-IR group than in the IR group. CONCLUSION: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury. | |
| 650 | 4 | |a Biológiai tudományok | |
| 650 | 4 | |a Általános orvostudomány | |
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| 700 | 0 | 1 | |a Szijártó Attila |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/29351/1/2704020.pdf |z Dokumentum-elérés |