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

作者：Keshari Kayvan R^*; Wilson David M; Sai Victor; Bok Robert; Jen Kuang Yu; Larson Peder; Van Criekinge Mark; Kurhanewicz John; Wang Zhen J

来源：Diabetes, 2015, 64(2): 344-352.

DOI：10.2337/db13-1829

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) C-13 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 C-13 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 C-13 DHA reduction to VitC with concomitant normalization of GSH concentration and Nox4 expression in diabetic mice. HP C-13 DHA enables rapid in vivo assessment of altered redox capacity in diabetic renal injury and after successful treatment.

• 出版日期2015-2