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Kidney Week

Abstract: PO2482

Chronic Aristolochic Acid Administrations Induce Renal Senescence in Mice

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Urate, Shingo, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Wakui, Hiromichi, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Tanaka, Shohei, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Abe, Eriko, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Tsukamoto, Shunichiro, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Taguchi, Shinya, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Suzuki, Toru, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Azushima, Kengo, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
  • Tamura, Kouichi, Yokohama City University Graduate School of Medicine Department of Medical Science and Cardiorenal Medicine, Yokohama, Japan
Background

The kidneys are one of the most susceptible organs to age-associated impairments. Recently, although renal aging research has been extensively performed, appropriate models of renal aging are still limited. Generally, renal aging is strongly associated with renal fibrosis, which is the final common pathway of chronic kidney disease. Aristolochic acid (AA), a renal toxic agent, causes aristolochic acid nephropathy (AAN) characterized by progressive renal fibrosis and functional decline. Here, we examined the potential of AAN as a model of renal senescence using chronic AA administrations into C57BL/6 mice.

Methods

8-week-old male C57BL/6 mice were assigned to AA or vehicle control group after 1-week acclimatization. Mice were intraperitoneally administered with AA (3mg/kg) or vehicle (75% dimethyl sulfoxide) twice a week for 4 weeks, followed by a 4-week recovery period.

Results

Compared to controls, the AA group showed aged kidney-like phenotypes such as renal atrophy, renal functional decline, and tubulointerstitial fibrosis. In addition, AA provoked cellular senescence specifically in the kidneys, concomitant with an increase in renal p16 mRNA expression and senescence-associated β-galactosidase activity. Additionally, AA-induced mice exhibited proximal tubular mitochondrial abnormalities, followed by accumulation of reactive oxygen species.

Conclusion

Collectively, the results of the present study indicates that AAN partially mimics aged kidney and could become a useful mouse model for kidney aging research.