MRI-based preclinical discovery of DILI: A lesson from paracetamol-induced hepatotoxicity

Abstract

Worldwide, drug-induced liver injury (DILI) is a major cause of hepatic failure. It is also the leading cause of withdrawal, cautionary labeling, and restricted usage of licensed drugs; therefore, European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) warn that the existing methods of assessing DILI are insufficient and that some of the translational biomarkers of hepatotoxicity must be relooked. Magnetic resonance imaging (MRI) seems to be a proper tool in elucidating the effects of DILI in both preclinical and clinical studies, providing excellent visualization of the morphology of the liver parenchyma. Therefore, herein, we propose preclinical MRI assessment of liver injury in experimental paracetamol-treated rats. Quantitative MRI clearly provides evidence of adverse effects in the liver tissue caused by a single overdose of paracetamol (1 g kg−1 and 1.5 g kg−1 b.w.). The results of the MRI were confirmed by the histopathological examination (H&E) of the rat liver specimen, however the adverse effects were not disclosed due to standard aminotransferase assays (ALT/AST) in rat blood serum. The results of our analysis demonstrate the successful application of MRI in the examination of paracetamol-induced hepatotoxicity in rats; it has a potential to serve as the early diagnostic tool for the prediction of DILI in preclinical evaluation.