Noninvasive biomarkers for acute hepatotoxicity induced by 1,3-dichloro-2-propanol: hyperpolarized 13C dynamic MR spectroscopy

Magn Reson Imaging. 2016 Feb;34(2):159-65. doi: 10.1016/j.mri.2015.10.023. Epub 2015 Oct 30.

Abstract

The purpose of this study was to investigate the cellular metabolite change for acute hepatotoxicity induced by 1,3-dichloro-2-propanol (1,3-DCP) in rats and its correlations with the enzyme levels. In order to induce acute hepatotoxicity, a single subcutaneous injection of 1,3-DCP (80 mg/kg) was given to six male Sprague-Dawley rats. Hyperpolarized (13)C dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-(13)C] pyruvate. The levels of serum aspartate am inotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in the 1,3-DCP treated rats were significantly increased as compared with those in normal rats. In the dynamic (13)C MR spectra, the ratios of [1-(13)C] lactate to the total carbon and [1-(13)C] alanine to the total carbon in the 1,3-DCP treated rats were significantly increased, and there were positive correlations between cellular metabolic changes and enzyme levels. The levels of [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity.

Keywords: 1,3-dichloro-2-propanol(1,3-DCP); Cellular metabolism; Dynamic nuclear polarization (DNP); Hepatotoxicity; Hyperpolarized (13)C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / metabolism*
  • Algorithms
  • Animals
  • Biomarkers / metabolism
  • Carbon-13 Magnetic Resonance Spectroscopy / methods*
  • Chemical and Drug Induced Liver Injury / diagnosis*
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Lactic Acid / metabolism*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Molecular Imaging / methods
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity
  • alpha-Chlorohydrin / analogs & derivatives*

Substances

  • Biomarkers
  • 1,3-dichloro-2-propanol
  • Lactic Acid
  • alpha-Chlorohydrin
  • Alanine