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Sci Rep. 2017 Apr 20;7:46014. doi: 10.1038/srep46014.

Hyperpolarized 13C Spectroscopic Evaluation of Oxidative Stress in a Rodent Model of Steatohepatitis.

Author information

1
Department of Radiology and Biomedical Imaging University of California, San Francisco, San Francisco, CA 94158, USA.
2
Department of Radiology Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
3
Molecular Pharmacology Program Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA.
4
Weill Cornell Medical College, New York, NY 10065, USA.

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, now considered the most common liver disease in the western world. Approximately one-third of patients with NASH develop non-alchoholic steatohepatitis (NASH), histologically defined by lobular and portal inflammation, and accompanied by marked oxidative stress. Patients with NASH are at increased risk for cirrhosis and hepatocellular carcinoma, and diagnosis currently requires invasive biopsy. In animal models of NASH, particularly the methionine-choline deficient (MCD) model, profound changes are seen in redox enzymes and key intracellular antioxidants. To study antioxidant status in NASH non-invasively, we applied the redox probe hyperpolarized [1-13C] dehydroascorbic acid (HP DHA), which is reduced to Vitamin C (VitC) rapidly in the normal liver. In MCD mice, we observed a significant decrease in HP DHA to VitC conversion that accompanied hepatic fat deposition. When these animals were subsequently placed on a normal diet, resonance ratios reverted to those seen in control mice. These findings suggest that HP DHA, a potentially clinically translatable imaging agent, holds special promise in imaging NASH and other metabolic syndromes, to monitor disease progression and response to targeted therapies.

PMID:
28425467
PMCID:
PMC5397869
DOI:
10.1038/srep46014
[Indexed for MEDLINE]
Free PMC Article

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