Abstract: TH-OR107

Mitochondria Homing Drug MA-5 Protects against Contrast Induced AKI

Session Information

  • Predicting AKI
    November 02, 2017 | Location: Room 282, Morial Convention Center
    Abstract Time: 06:18 PM - 06:30 PM

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational


  • Suzuki, Takehiro, Tohoku university, Sendai, Japan
  • Matsuhashi, Tetsuro, Tohoku university, Sendai, Japan
  • Matsuo, Akihiro, Tohoku university, Sendai, Japan
  • Kikuchi, Koichi, Tohoku university, Sendai, Japan
  • Mishima, Eikan, Tohoku university, Sendai, Japan
  • Suzuki, Chitose, Tohoku university, Sendai, Japan
  • Ito, Sadayoshi, Tohoku university, Sendai, Japan
  • Abe, Takaaki, Tohoku university, Sendai, Japan

Contrast induced acute kidney injury (CI-AKI) is the common cause of the iatrogenic and drug-induced kidney injury, but the therapeutic procedures have not been established. The renal hypoxia and the toxic effects on renal tubular cells are postulated as the pathophysiologic mechanisms of CI-AKI. Recently we reported mitochondria homing drug, mitochonic acid-5 (MA-5) increased intracellular ATP, decreased mitochondrial ROS and improved cell survivals of fibroblasts form mitochondrial disease patients by binding mitochondrial protein Mitofilin and promoting oligomelization of ATP synthases (Suzuki T. Tohoku J Exp Med 2015, Matushashi T. EBioMedicine 2017). MA-5 improved the renal function and tubular cell injuries in murine renal ischemia reperfusion and cisplatin induced nephropathy models (Suzuki T. JASN 2016). The aim of this study is to examine the protective effects of MA-5 on CI-AKI.


Human proximal tubular cell line HK-2 cells were cultured to 80% confluent and MA-5 at 10uM final concentration for 24hr without serum and then added radiocontrasts sodium ditrizoate, Iopamidol and iohexol at 75mg iodine /ml for another 1hr. Cell viability and cytotoxicity were accessed by WST-8 assay and LDH assay respectively. Male CD-1 and C57/BL6 mice, 10-12 week old were left-nephrectomized (Nx) and MA-5 was administrated, at 50mg/kg body weight by gavage, to mice 2hr before they injected with an inhibitor of prostaglandin synthesis (indomethacin, 10 mg/kg) intraperitoneally and iohexol (300 mg iodine/ml, 2 g iodine/kg ) intravenously. 24hr after iohexol injection, mice were sacrificed, serum creatinine (Cr), urinary Neutrophil gelatinase-associated lipocalin (NGAL) and renal pathology were examined.


MA-5 improved cell viabilities and reduced injured cell derived LDH activity in culture medium in Sodium ditrizoate, Iopamidol and iohexol treated HK2 cell culture. Serum Cr at 24hr after iohexol injection showed tendency to improve but not significant in MA-5 treated mice comapred to control group. Urinary NGAL was significantly decreased in MA-5 treated animals compared to vehicle gavaged mice.


MA-5 exhibited improved viability in contrast medium treated HK-2 cells as well as decrease renal injury marker NGAL in CI-AKI model mice. MA-5 might have the therapeutic potency on CI-AKI.


  • Government Support - Non-U.S.