Figure 1
From: Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat
Experimental design to measure early perturbations in rat liver metabolism. Preliminary studies using clinical chemistry markers to determine acetaminophen (APAP) dose and duration. Alterations in ALT (a) and AST activity levels (b) for control (dashed line with circles, n = 6), 1 g/kg APAP (solid line with triangles, n = 6), and 2 g/kg APAP (dotted line with squares, n = 7, *p < 0.05). (c) Schematic showing the design of the study, using Sprague Dawley rats exposed to a single dose of 2 g/kg of APAP under fasting conditions. In Study 1, rats were administered APAP and observed for 10 h (n = 8) together with control animals (n = 8), after which they were infused with 2H/13C labeling to obtain flux measurements using metabolic flux analysis. In Studies 2 and 3, rats were given APAP and observed for 5 h (n = 8) and 10 h (n = 8), respectively, with the corresponding control groups treated with vehicle (n = 8 each). Samples of blood and liver tissue were collected at 5 h or 10 h after APAP exposure and subjected to global metabolic profiling analysis or RNA sequencing, respectively (See Materials and Methods for further details).
