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Optical Metabolic Imaging for Assessment of Radiation-Induced Injury to Rat Kidney and Mitigation by Lisinopril

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Abstract

The kidney is one of the most radiosensitive organs; it is the primary dose-limiting organ in radiotherapies for upper abdominal cancers. The role of mitochondrial redox state in the development and treatment of renal radiation injury, however, remains ill-defined. This study utilizes 3D optical cryo-imaging to quantify renal mitochondrial bioenergetics dysfunction after 13 Gy leg-out partial body irradiation (PBI). Furthermore, the mitigating effects of lisinopril (lisino), an anti-hypertensive angiotensin converting enzyme inhibitor, is assessed in renal radiation-induced injuries. Around day 150 post-irradiation, kidneys are harvested for cryo-imaging. The 3D images of the metabolic indices (NADH, nicotinamide adenine dinucleotide, and FAD, flavin adenine dinucleotide) are acquired, and the mitochondrial redox states of the irradiated and irradiated + lisino kidneys are quantified by calculating the volumetric mean redox ratio (NADH/FAD). PBI oxidized renal mitochondrial redox state by 78%. The kidneys from the irradiated + lisino rats showed mitigation of mitochondrial redox state by 93% compared to the PBI group. The study provides evidence for an altered bioenergetics and energy metabolism in the rat model of irradiation-induced kidney damage. In addition, the results suggest that lisinopril mitigates irradiation damage by attenuating the oxidation of mitochondria leading to increase redox ratio.

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Acknowledgment

We thank Brian Fish, Jayashree Narayanan, Tracy Gasperetti, and James Heisner for excellent animal care, irradiation, dosimetry and tissue harvesting. We also are thankful for funding support from UWM RGI 101X290 and 101 × 397, NIAID R01-101898, U01-107305, U01AI33594, Department of Radiation Oncology, Cardiovascular and Cancer Centers at MCW and NIH grant R01HL116530.

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Author notes

  1. Amadou K. S. Camara and Mahsa Ranji are co-senior authors.

Authors and Affiliations

  1. Department of Electrical Engineering, Biophotonics Lab, University of Wisconsin Milwaukee, Milwaukee, WI, USA

    Shima Mehrvar, Mette Funding la Cour & Mahsa Ranji

  2. Department of Radiation Oncology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Meetha Medhora

  3. Department of Anesthesiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Amadou K. S. Camara

  4. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Meetha Medhora & Amadou K. S. Camara

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  1. Shima Mehrvar
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Correspondence to Amadou K. S. Camara or Mahsa Ranji.

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Mehrvar, S., la Cour, M.F., Medhora, M. et al. Optical Metabolic Imaging for Assessment of Radiation-Induced Injury to Rat Kidney and Mitigation by Lisinopril. Ann Biomed Eng 47, 1564–1574 (2019). https://doi.org/10.1007/s10439-019-02255-8

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