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Abstract: FR-PO189

Reno-Protective Effect of Haptoglobin and Hemopexin by Inhibiting Ferroptosis in Ischemic Reperfusion AKI

Session Information

  • AKI: Mechanisms - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Ko, Ye Eun, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Nam, Boyoung, Institute of Kidney Disease Research, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kim, Gyu Ri, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Ryu, Jaejin, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kim, Hyung Woo, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Park, Jung Tak, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Han, Seung Hyeok, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Kang, Shin-Wook, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
  • Yoo, Tae-Hyun, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea (the Republic of)
Background

Recent studies showed that cell free hemoglobin (CFH) increases in patients with sepsis and after heart surgery, which may cause acute kidney injury (AKI). Since CFH contains catalytically active iron, iron-dependent cell death, CFH related iron-dependent cell death, ferroptosis may induce AKI. This study investigates the reno-protective effect of haptoglobin (Hp) and hemopexin (Hx), which scavenge CFH, in an experimental AKI model.

Methods

Ischemic reperfusion injury (IRI) animal models were used as AKI animal models. After 2, 4, 6, 8, and 24 hours, CFH and hemin levels were evaluated in both the control and IRI groups. In addition, the IRI models were treated with different doses (25, 50, 100, and 200 mg/kg) of Hp or Hx via intravenous injection 30 minutes prior to IRI surgery. CFH, hemin, and kidney injury markers, as well as an oxidative stress marker, and ferroptosis markers were evaluated 24 hours later. Furthermore, kidney injury score was evaluated from kidney tissues based on the percentage of cell necrosis, loss of brush border, cast formation, and tubule dilatation.

Results

CFH and hemin levels increased in the IRI group at each hour compared to the control. Injection of Hp decreased CFH levels regardless of the dosage, while injection of Hx decreased hemin levels compared to the IRI group. Creatinine, BUN, NGAL, and MDA levels showed increases in the IRI group compared to the control. Treatment with Hp or Hx resulted in decreases in creatinine, BUN, MDA, and kidney injury score across all dosage compared to the IRI group. NGAL levels showed a decrease in all drug injection groups except for the Hp 25mg/kg group compared to the IRI group. In the IRI group, the mRNA expression of cystine/glutamate antiporter system Xc− decreased compared to the control, while ferritin heavy chain 1 increased. However, treatment with Hp or Hx resulted in an increase in cystine/glutamate antiporter system Xc− mRNA expression and a decrease in ferritin heavy chain 1 compared to the IRI group.

Conclusion

Hp and Hx, scavenger proteins, may aid as preventive agents for ischemic reperfusion AKI by inhibiting ferroptosis.