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Abstract: TH-PO015

Alpha-1 Acid Glycoprotein Ameliorates Hemolysis-Induced Renal Oxidative Stress Via Accelerating Plasma Free Hemoglobin Clearance Through CD163 Induction

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Fujimura, Rui, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto-shi, Japan
  • Watanabe, Hiroshi, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto-shi, Japan
  • Nishida, Kento, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto-shi, Japan
  • Bi, Jing, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto-shi, Japan
  • Maruyama, Toru, Department of Biopharmaceutics, School of Pharmacy, Kumamoto University, Kumamoto-shi, Japan
Background

In hemolysis-induced kidney disease such as paroxysmal nocturnal hemoglobinuria, increased free hemoglobin (Hb) contributes to the renal vascular endothelium injury and renal oxidative stress which play a role in the progression of AKI and CKD. In hemolytic condition, CD163, hemoglobin scavenger receptor, expressed on monocytes and macrophages takes up plasma free Hb or Hb-haptoglobin (Hp) complex. We previously found that the an acute-phase protein, alpha-1 acid glycoprotein (AGP) increased the expression of CD163 in macrophages (Komori et al. J Biol Chem 2012). The purpose of this study is to investigate the effect of exogenously administered AGP on plasma free Hb level and renal oxidative stress in hemolysis-model mice.

Methods

Hemolysis model mice were generated by intraperitoneally administered phenylhydrazine (PH). AGP was intraperitoneally administered at 24 hr and 48 hr before PH administration. The mice were sacrificed at 24 hr after PH administration.

Results

Administration of AGP to PH mice reduced plasma free Hb level and renal oxidative stress (malondialdehyde). In the same experimental condition, we found that AGP treatment increased CD163 expression in kidney and liver. In healthy mice, administration of AGP also increased the expression of CD163 in kidney and liver, but it did not affect the plasma Hp level. These data suggested that the effect of AGP on free Hb clearance could be due to the induction of CD163. In vitro experiments using human monocyte-derived macrophages (dTHP-1 cells), AGP treatment increased the expression of CD163 and also increased the intracellular uptake of Hb-Hp complex.

Conclusion

AGP ameliorates hemolysis-induced renal oxidative stress via accelerating plasma free hemoglobin clearance through CD163 induction.