Attenuation of skeletal muscle and renal injury to the lower limb following ischemia-reperfusion using mPTP inhibitor NIM-811

David Garbaisz, Zsolt Turoczi, Peter Aranyi, Andras Fulop, Oliver Rosero, E. Hermesz, Agnes Ferencz, G. Lotz, Laszlo Harsanyi, Attila Szijarto

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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-α 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+: 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

Original languageEnglish
Article numbere101067
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 26 2014

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ischemia
limbs (animal)
Surgery
Reperfusion
Muscle
skeletal muscle
Lower Extremity
permeability
Skeletal Muscle
Ischemia
surgery
kidneys
Kidney
Wounds and Injuries
rhabdomyolysis
muscles
Mitochondria
Peroxynitrous Acid
cyclosporine
Isoleucine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Attenuation of skeletal muscle and renal injury to the lower limb following ischemia-reperfusion using mPTP inhibitor NIM-811. / Garbaisz, David; Turoczi, Zsolt; Aranyi, Peter; Fulop, Andras; Rosero, Oliver; Hermesz, E.; Ferencz, Agnes; Lotz, G.; Harsanyi, Laszlo; Szijarto, Attila.

In: PLoS One, Vol. 9, No. 6, e101067, 26.06.2014.

Research output: Contribution to journalArticle

Garbaisz, David ; Turoczi, Zsolt ; Aranyi, Peter ; Fulop, Andras ; Rosero, Oliver ; Hermesz, E. ; Ferencz, Agnes ; Lotz, G. ; Harsanyi, Laszlo ; Szijarto, Attila. / Attenuation of skeletal muscle and renal injury to the lower limb following ischemia-reperfusion using mPTP inhibitor NIM-811. In: PLoS One. 2014 ; Vol. 9, No. 6.
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AU - Fulop, Andras

AU - Rosero, Oliver

AU - Hermesz, E.

AU - Ferencz, Agnes

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AU - Szijarto, Attila

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