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 reduction-oxidation (redox) sensor, hyperpolarized (HP) (13)C 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 (13)C 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 (13)C DHA reduction to VitC with concomitant normalization of GSH concentration and Nox4 expression in diabetic mice. HP (13)C DHA enables rapid in vivo assessment of altered redox capacity in diabetic renal injury and after successful treatment.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY rahimikk@mskcc.org.
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Keshari
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Victor
authors.initials: V
authors.lastname: Sai
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bok
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Kuang-Yu
authors.initials: KY
authors.lastname: Jen
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Peder
authors.initials: P
authors.lastname: Larson
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Criekinge
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.affiliation: Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
authors.forename: Zhen J
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D003683:Dehydroascorbic Acid / Q000737:chemistry / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005978:Glutathione; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D054411:Receptors, Leptin
chemical_list: D002247:Carbon Isotopes; D054411:Receptors, Leptin; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D005978:Glutathione; D003683:Dehydroascorbic Acid