| Autor: |
Baligand, Celine, Qin, Hecong, True‐Yasaki, 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 |
| Zdroj: |
NMR in Biomedicine; Oct2017, Vol. 30 Issue 10, pn/a-N.PAG, 1590p |
| Abstrakt: |
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) 13C dehydroascorbate (DHA) and 13C 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 13C 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 13C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13C lactate/pyruvate ratio at day 7 compared with baseline, although the 13C 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 13C MRS for the non-invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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