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<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-α and IL-6 levels were significantly 
lower (TNF-α: 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.