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NMR Biomed. 2017 Oct;30(10). doi: 10.1002/nbm.3765. Epub 2017 Jul 14.

Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.

Author information

1
Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
2
Medicine, San Francisco VAMC/University of California San Francisco, San Francisco, California, USA.

Abstract

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13 C dehydroascorbate (DHA) and 13 C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham-operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13 C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13 C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13 C lactate/pyruvate ratio at day 7 compared with baseline, although the 13 C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham-operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13 C MRS for the non-invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI.

KEYWORDS:

Acute kidney injury; [1−13C]dehydroascorbic acid; [1−13C]pyruvate; hyperpolarization; magnetic resonance spectroscopy; mitochondrial dysfunction; oxidative stress

PMID:
28708304
PMCID:
PMC5618802
DOI:
10.1002/nbm.3765
[Indexed for MEDLINE]
Free PMC Article

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