The functional and ultrastructural changes of hepatic mitochondria in acute experimental pancreatitis in dogs treated with prostacyclin

Abstract

Acute pancreatitis affects the subcellular status of the liver both by enzymatic toxemia and by the impairment of the protective function exerted by a normal pancreas on the liver. The aim of this study was to investigate the effect of the cytoprotective agent prostacyclin (PGI 2 ) on hepatic mitochondria during acute experimental pancreatitis (AEP) in dogs. AEP was induced by the injection of a bile and trypsin mixture into the pancreatic duct, and experiments were terminated after 12 hrs with the exception of dogs with AEP 24 hrs (N = 5). The hepatic mitochondria from the group with AEP 12 hrs without treatment (N = 5) showed a significant impairment of succinate oxidation in St. 3 (with ADP) to 20.1 nanoatoms O×min −1 × mg −1 of mitochondrial protein in comparison to healthy dogs (N = 4) −37.6 units. The respiratory control ratio (RCR) in the former group was half as great as in the control group (1.56 and 3.13 respectively). The ADP: 0 ratio in this group was impossible to calculate. DNP-stimulated ATP-ase activity was lowered to 50.6 nM Pi min −1 mg −1 of protein in comparison to the healthy animals (642.7 units). In dogs AEP 12 hrs treated with PGI 2 in the dose of 20 ng/kg · min for 12 hrs (N = 5) and in the group additionally pretreated with PGI 2 for 1 hr before AEP (N = 5), the respective values of succinate oxidation in St. 3 were 22.2 and 26.5 units; RCR with ADP 2.05 and 2.07; ADP: O ratio 1.10 and 1.19 (in healthy dogs ADP: O = 1.90). DNP-stimulated ATP-ase activity was also augmented in comparison with the untreated group, 94.0 and 125.6 units, respectively. In the group with AEP 12 hrs without treatment, the ultrastructural examination of the liver showed severely damaged, mitochondria with swelling, destruction of limiting membranes and cristae. In the group with AEP 24 hrs without treatment the functional and morphological picture of mitochondria was improved in comparison to AEP 12 hrs and was comparable to treated groups. Prostacyclin in investigated dosage exerts a protective effect on hepatic mitochondria, damaged during acute experimental pancreatitis in dogs.