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Kidney Week

Abstract: PO0250

A Combination of Contrast Media and Radiation Increases DNA Damage and Delays DNA Damage Repair in Mouse Kidneys

Session Information

  • AKI Mechanisms - 3
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Fujino, Shu, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Doi, Shigehiro, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Doi, Toshiki, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Nakashima, Ayumu, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Masaki, Takao, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
Background

Contrast-induced nephropathy (CIN), resulting from contrast media (CM) administration, is a major complication of angiographic procedures. CIN may also be induced by exposure to radiation. However, the molecular mechanism of CIN has only been investigated using a CM-injected rodent model. Here, we examined the dual effect of CM and irradiation (IR) on DNA damage and repair in in vitro and in vivo.

Methods

Human renal tubular epithelium (HK)-2 cells were stimulated by medium containing 100 mg iodine/ml of iohexol (Ihx-HK2), 1 Gy of X-ray irradiation (IR-HK2), or both (Ihx+IR-HK2). Mannitol-treated cells were used as an experimental control (Man-HK2 or Man+IR-HK2). For the in vivo study, ischemic reperfusion injury (IRI) was induced in mice after right kidney removal, then IRI mice were treated with 200 µL iohexol (IRI/CIN) and/or 10 Gy X-ray irradiation (IRI+IR or IRI/CIN+IR). We performed immunohistochemistry, immunofluorescence staining, and western blotting for DNA damage markers (γH2AX, pATM, 53BP1, and RAD51), an oxidative stress marker (8-OHdG), a macrophage marker (F4/80), and klotho.

Results

Immunofluorescence staining revealed increased expression of γH2AX, 53BP1, and RAD51 in Ihx+IR-HK2 compared with Ihx- or IR-HK2. These proteins remained highly expressed at 24 h in Ihx+IR-HK2, but not in Ihx- or IR-HK2. Cells positive for γH2AX, pATM, 53BP1, and RAD51 were significantly increased in IRI/CIN+IR mice, and 8-OHdG and F4/80 expression was also remarkably increased, whereas that of klotho was decreased in IRI/CIN+IR mouse kidneys.

Conclusion

Both CM administration and exposure to radiation induce DNA damage and delay DNA damage repair, which are accompanied by increased levels of oxidative stress and inflammation and downregulation of klotho expression.