Preservation of obese rat livers by subnormothermic machine perfusion protects dipeptidylpeptidase–IV activity and expression in the biliary tree.

Background and aim: We previously documented that machine perfusion at subnormothermic temperature (20°C; MP20) improves the preservation of hepatocytes and sinusoidal cells of normal and marginal liver respect to conventional cold storage (CS)1. We report the activity and expression of dipeptidylpeptidase-IV (DPP-IV) in the biliary tree of fatty livers preserved with CS or MP20 and reperfused as compared to control fatty liver. M&M: Adult obese (fa/fa) Zucker rats. MP20: livers perfused for 6 h with oxygenated Krebs-Henseleit solution (KH) pH 7.4 at 20°C. CS: livers perfused in situ and preserved with UW solution at 4°C for 6 h. Reperfusion with KH (2 h at 37°C). DPP-IV activity: azo-coupling method. DPP-IV expression: immunoperoxidase method (clone 5E8). Results. Control liver: Intense enzyme activity in the whole biliary tree; distorted bile canaliculi in steatotic hepatocytes. Canalicular immunoreactivity present mainly in periportal hepatocytes, suggesting that the enzyme reaction demonstrates other peptidases acting on the same substrate. CS: Edema, cell death and dilated canaliculi and sinusoids especially in the mid-zone where enzyme- and immunoreactivity were much lower than in the controls; Hering canals and ducts reactions as in the controls. MP20: Morphology much better preserved respect to CS. DPP-IV activity and immunoreactivity similar to the controls. Conclusions: Being DPP-IV a key enzyme for the catabolism of incretins and neuropeptides, its preservation by MP20 is a good premise for the resume of functionality of the bile tree of fatty liver after transplantation. 1Vairetti et al. Liver Transpl. 15:20-29, 2009.