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Noninvasive In Vivo Imaging of Diabetes-Induced Renal Oxidative Stress and Response to Therapy Using Hyperpolarized 13C Dehydroascorbate Magnetic Resonance

Keshari, Kayvan R., Wilson, David M., Sai, Victor, Bok, Robert, Jen, Kuang-Yu, Larson, Peder, Van Criekinge, Mark, Kurhanewicz, John, Wang, Zhen J.·2015·Diabetes
DOI 10.2337/db13-1829PMC PMC4303960
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Abstract

Oxidative stress has been proposed to be a unifying cause for diabetic nephropathy and a target for novel therapies. Here we apply a new endogenous reduction-oxidation (redox) sensor, hyperpolarized (HP) 13C dehydroascorbate (DHA), in conjunction with MRI to noninvasively interrogate the renal redox capacity in a mouse diabetes model. The diabetic mice demonstrate an early decrease in renal redox capacity, as shown by the lower in vivo HP 13C DHA reduction to the antioxidant vitamin C (VitC), prior to histological evidence of nephropathy. This correlates with lower tissue reduced glutathione (GSH) concentration and higher NADPH oxidase 4 (Nox4) expression, consistent with increased superoxide generation and oxidative stress. ACE inhibition restores the HP 13C DHA reduction to VitC with concomitant normalization of GSH concentration and Nox4 expression in diabetic mice. HP 13C DHA enables rapid in vivo assessment of altered redox capacity in diabetic renal injury and after successful treatment.

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Cited by

Metadata

Authors
Keshari, K. R., Wilson, D. M., Sai, V., Bok, R., Jen, K.-Y., Larson, P., Van Criekinge, M., Kurhanewicz, J., & Wang, Z. J.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2014-09-02
Volume
64
Issue
2
Pages
344-352
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/db13-1829
PMC
PMC4303960
Cited by
59
References
2
Language
en
Licence
www.diabetesjournals.org/site/license (vor, 333 d)
Funders
Institut national de la santè et de la recherche mèdicale (P41EB013598, R00EB012064, R00EB014328, R01CA166766)

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