Lysosomal-mitochondrial interrelationships in damage to the liver in acute experimental pancreatitis in dogs. Treatment with prostacyclin (PGI₂)

Summary

In acute pancreatitis, damage to the liver is an important aspect of multiorgan failure. In 28 dogs (20 with bile-trypsin induced acute experimental pancreatitis (AEP)), ‘total’ and ‘free’ activity of lysosomal hydrolases: β-glucuronidase, cathepsins and acid phosphatase in mitochondrial and lysosomal subfraction of the liver were determined 12 h or 24 h after the induction of AEP. The respiratory control ratio with sodium succinate as a substrate, using Clarck's electrode and uncoupler-dependent ATP-ase activity in mitochondrial subfraction, was assayed. Groups of dogs were treated or pretreated with prostacyclin (PGI₂), 20 ng·kg⁻¹·min⁻¹ 1.v. for 12 or 13 h. The relative free activity of hydrolases was significantly elevated in untreated AEP after 12 h and was partially normalized in AEP after 24 h or after 12 h followed by treatment and pretreatment with PGI₂. Respiratory control ratio was twice lower than normal in AEP after 12 h and partially normalized after 24 h post PGI₂ treatment. The relative free activity of lysosomal hydrolases was highly negatively correlated with respiratory control ratio. It was concluded, that during AEP in dogs the function of liver mitochondria and lysosomal stability are impaired. The significant correlation found between the mitochondrial and lysosomal lesions points to lysosomal-mitochondrial interactions in liver damage in AEP. Prostacyclin in the investigated dose partially prevents the mitochondrial and lysosomal lesions in liver in this disease.