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Kidney Week

Abstract: FR-PO147

Mitochondrial Infusion Attenuates Cisplatin-Induced AKI by Inducing Mitochondrial Dynamics

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

  • Afjal, Mohammad Amir, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Stayton, Amanda Shea, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Horton, Thomas W., The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Mazumdar, Soumi, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Wajidunnisa, Fnu, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Kuscu, Canan, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Kuscu, Cem, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
  • Pabla, Navjot, The Ohio State University, Columbus, Ohio, United States
  • Bajwa, Amandeep, The University of Tennessee Health Science Center Department of Surgery, Memphis, Tennessee, United States
Background

Acute kidney injury (AKI) is a critical clinical condition of hospitalization with high mortality. Approximate 30% of patients treated with cisplatin (CP) develop AKI. CP affects mainly proximal tubular cells as well as tubular mitochondria and several mechanisms have been involved such as oxidative stress, apoptosis, and mitochondrial damage which leads to AKI. Mitochondrial function and homeostasis is crucial for the maintenance of renal function. In the current study, we evaluated the use of mitochondrial infusion, which could be a promising strategy to prevent CP-induced AKI. Currently it is unknown whether mitochondrial infusion will reduce alterations in mitochondria bioenergetics and dynamics in CP-induced AKI.

Methods

10-12 wks old male mice were divided into four groups. Group I = saline, group II = 20 mpk CP, group III and IV received 20 mg/kg or 50 µg/mouse isolated healthy liver mitochondria via I.V. injection 24 hrs after CP injection (Fig 1A).

Results

Mice receiving either low dose 50 µg/mouse or high dose 20 mg/kg mitochondria had significantly reduced plasma BUN (Fig 1B) and creatinine including renal injury markers (Kim1 and Ngal). The inflammatory genes such as Tnfa (Fig 1C), Il6, Ilb, Mcp1 induced by CP were significantly reduced in both groups III and IV. Treatment with mitochondria significantly increased mitochondrial biogenesis genes Pgc1alpha, mitochondrial transcription factor A (Tfam) and antioxidant marker Nrf2 compared to CP group.

Conclusion

Our results demonstrate that mitotherapy protects from renal injury in CP induced model of AKI. This study indicating that mitochondrial infusion could be promising therapy to protect kidneys from CP induced AKI.