Noninvasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized 13C dehydroascorbate magnetic resonance

Kayvan R. Keshari, David M. Wilson, Victor Sai, Robert Bok, Kuang-Yu Jen, Peder Larson, Mark Van Criekinge, John Kurhanewicz, Zhen J. Wang

Research output: Contribution to journalArticle

37 Scopus citations

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 reductionoxidation (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.

Original languageEnglish (US)
Pages (from-to)344-352
Number of pages9
JournalDiabetes
Volume64
Issue number2
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Noninvasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized <sup>13</sup>C dehydroascorbate magnetic resonance'. Together they form a unique fingerprint.

  • Cite this

    Keshari, K. R., Wilson, D. M., Sai, V., Bok, R., Jen, K-Y., Larson, P., Van Criekinge, M., Kurhanewicz, J., & Wang, Z. J. (2015). Noninvasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized 13C dehydroascorbate magnetic resonance. Diabetes, 64(2), 344-352. https://doi.org/10.2337/db13-1829