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Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model
Author(s) -
Baligand Celine,
Qin Hecong,
TrueYasaki Aisha,
Gordon Jeremy W.,
Morze Cornelius,
Santos Justin Delos,
Wilson David M.,
Raffai Robert,
Cowley Patrick M.,
Baker Anthony J.,
Kurhanewicz John,
Lovett David H.,
Wang Zhen Jane
Publication year - 2017
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.3765
Subject(s) - oxidative stress , endocrinology , medicine , ischemia , kidney , chemistry , pyruvate dehydrogenase complex , reactive oxygen species , vitamin c , reperfusion injury , kidney disease , magnetic resonance imaging , renal ischemia , acute kidney injury , biochemistry , enzyme , radiology
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.