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...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Garbaisz Dávid
Turóczi Zsolt
Arányi Péter
Fülöp András
Rosero Olivér
Hermesz Edit
Ferencz Ágnes
Lotz Gábor
Harsányi László
Szijártó Attila
Dokumentumtípus: Cikk
Megjelent: 2014
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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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 
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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 
700 0 1 |a Turóczi Zsolt  |e aut 
700 0 1 |a Arányi Péter  |e aut 
700 0 1 |a Fülöp András  |e aut 
700 0 1 |a Rosero Olivér  |e aut 
700 0 1 |a Hermesz Edit  |e aut 
700 0 1 |a Ferencz Ágnes  |e aut 
700 0 1 |a Lotz Gábor  |e aut 
700 0 1 |a Harsányi László  |e aut 
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