The role of lysosomal alterations in the damage to the pancreas and liver in acute experimental pancreatitis in dogs.
The role of lysosomal hydrolases in the pathogenesis of acute pancreatitis and secondary liver injury, as an important aspect of multisystem organ failure, remains unclear. The purpose of this study was to assess the lysosomal fragility in both organs in acute experimental pancreatitis (AEP) of graded severity in dogs. In 7 dogs, the moderate (M) and in 13 dogs severe (S) variant of bile--trypsin AEP--was induced; 6 dogs were in control group (C). The 24 h survival time was 6/7 and 6/13, respectively. After that time, the dogs were sacrificed and the lysosomal enriched subfraction (L) from both organs was isolated by ultracentrifugation. The total (T) and free (F) activities of beta-glucuronidase (beta G), cathepsins (Cs) and acid phosphatase (AcP) according to Gianetto and de Duve were assayed. The fractional free activity (% F/T) was adapted as and index of lysosomal stability. The %F/T of BG in the homogenate of the pancreas in AEP(S) was higher than that in AEP(M) (92% vs. 71%, p < 0.05, and vs. 37% in C, p < 0.005). The %F/T of Cs and AcP showed a similar pattern. The %F/T of beta G in L of the liver in AEP(S) was 38% vs. 29% in AEP(M), (p < 0.05), and vs. 20% in C (p < 0.05). In AEP in dogs the %F/T activities of lysosomal hydrolases in the pancreas and liver were increased, suggesting the labilization of lysosomal membranes in severe form of this disease. Our results support the pathogenic role of lysosomal hydrolases in the damage to the pancreas and liver in acute pancreatitis.
Długosz
J W
JW
Department of Gastroenterology, Medical Academy, Białystok, Poland.
Triebling
A T
AT
Brzozowski
J
J
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006867:Hydrolases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000503:physiopathology; D008247:Lysosomes / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000201:enzymology* / Q000503:physiopathology; D010195:Pancreatitis / Q000201:enzymology* / Q000503:physiopathology
D006867:Hydrolases; D000681:Amylases