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

   

Authors:	Keshari, K. R.; Wilson, D. M.; Sai, V.; Bok, R.; Jen, K. Y.; Larson, P.; Van Criekinge, M.; Kurhanewicz, J.; Wang, Z. J.
Article Title:	Noninvasive in vivo imaging of diabetes-induced renal oxidative stress and response to therapy using hyperpolarized 13C dehydroascorbate magnetic resonance
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.
Keywords:	controlled study; protein expression; treatment response; unclassified drug; nonhuman; nuclear magnetic resonance imaging; mouse; enzyme inhibition; animal experiment; animal model; diabetes mellitus; diabetic nephropathy; oxidative stress; ascorbic acid; dehydroascorbic acid; oxidation reduction reaction; glutathione; carbon 13; dipeptidyl carboxypeptidase; male; priority journal; article; carbon 13 dehydroascorbate; reduced nicotinamide adenine dinucleotide phosphate oxidase 4
Journal Title:	Diabetes
Volume:	64
Issue:	2
ISSN:	0012-1797
Publisher:	American Diabetes Association
Date Published:	2015-02-01
Start Page:	344
End Page:	352
Language:	English
DOI:	10.2337/db13-1829
PROVIDER:	scopus
PMCID:	PMC4303960
PUBMED:	25187363
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84921932256&partnerID=40&md5=e73fc33d395c6db0d995d83eff6769dc
Notes:	Export Date: 2 March 2015 -- Source: Scopus

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