Energy metabolism of pancreatic mitochondria in experimental acute pancreatitis

A disturbed energy metabolism in pancreatic acinar cells is discussed as factor contributing to the development of acute pancreatitis (AP). In this study, we investigated to what extent the mitochondrial ATP producing capacity is impaired in the pancreatic tissue of rats with experimental AP. For preparation of mitochondria from rat pancreas, routine isolation procedures (tissue homogenization and differential centrifugation) were applied. Mitochondria were isolated from rats,vith edematous pancreatitis, produced by hyperstimulation with caerulein, and from rats with mild necrotizing acute pancreatitis. The latter form of AP was induced by a temporary occlusion of the biliary pancreatic duct accompanied by a simultaneous intravenous injection of caerulein plus secretin and an intraabdominal administration of ethanol. As functional parameters of oxidative phosphorylation, the respiration rate, the mitochondrial membrane potential, and the actvity of the complex I of the respiratory chain wire determined. Mitochondria from rats with caerulein AP showed an enhanced respiration (61% vs. saline control) and a diminished membrane potential (-17 mV) if respiring,vith succinate in the non-phosphorylating state. This indicates an increased proton leak across the mitochondrial inner membrane. In the mild necrotizing AP, mitochondria were characterized by a decreased respiration with NAD(+)-linked substrates (-33% vs. sham-operated animals). This inhibition of respiration was confirmed by the reduced activity measured for the NADH-cytochrome c reductase (-32%). In both models of experimental AP the potency of mitochondria to produce ATP was significantly diminished. The stronger impairment of mitochondrial functions were found in the necrotizing form of AP. Reactive oxygen species may lead to the observed alterations to the enhanced permeability of the mitochondrial inner membrane as well as to the inhibition,of the complex I of the respiratory chain.