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

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 C-13 dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-C-13] pyruvate. The levels of serum aspartate aminotransferase (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 C-13 MR spectra, the ratios of [1-C-13] lactate to the total carbon and [1-C-13] 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-C-13] lactate and [1-C-13] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity. (C) 2015 Elsevier Inc. All rights reserved.