Purpose: In this study, we developed an ex vivo functional assay to assess liver metabolic capacity adapted from the lidocaïne test in rats.
Methods: Animals used were subjected to different models of liver injury: hypothermic ischemia (H/I, n = 8), ischemia-reperfusion (I/R, n = 8) and CCl4 induced liver cirrhosis (n = 11), and compared with sham operated rats (n = 5). Livers were then extracted and a fragment of whole tissue was incubated with lidocaïne for 15, 30, 60, 120, 240, 360, and 720 min at which both lidocaïne and its major metabolite monoethylglycinexylidide (MEGX) were measured by high performance liquid chromatography (HPLC). A histological study and biochemical assays (transaminase levels) were also performed to further evaluate and confirm our data.
Results: Pharmacokinetic profile of lidocaïne metabolism in sham-operated animals revealed that the maximum concentration of MEGX is achieved at 120 min. Both lidocaïne metabolism and MEGX formation levels were significantly altered in all three models of hepatic injury. The extent of hepatic damage was confirmed by increased levels of transaminase levels and alteration of hepatocyte's structure with areas of necrosis.
Conclusion: Our method provides reliable and reproducible results using only a small portion of liver which allows for a fast and easy assessment of liver metabolic capacity. Moreover, our method presents an alternative to the in vivo technique and seems more feasible in a clinical setting.
Keywords: Cirrhosis; Ex vivo; Hypothermic ischemia; Ischemia-reperfusion; Liver metabolism; MEGX.