glycodeoxycholic-acid and Hemorrhage

Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest.. Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined.. Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation.. Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.

Topics: Animals; Antioxidants; Ceruletide; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione Peroxidase; Glycodeoxycholic Acid; Hemorrhage; Infusions, Intravenous; Injections, Intravenous; Lipid Peroxidation; Male; Octreotide; Pancreas; Pancreatitis, Acute Necrotizing; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Time Factors

alpha 1-Acid glycoprotein (AAG), a highly negatively charged glycoprotein, well known for its capillary stabilizing effect, was tested in rat models of acute edematous pancreatitis, acute hemorrhagic-necrotizing pancreatitis, and acute respiratory distress syndrome (ARDS). In cerulein-elicited edematous pancreatitis AAG improved histological alterations at 200 mg/kg i.v. and plasma amylase activity at 1800 or 4200 mg/kg i.v. All other parameters (edema, plasma lipase) were not affected in a biologically relevant manner. In glycodeoxycholic acid-induced hemorrhagic-necrotizing pancreatitis AAG was without effect on parameters measured (plasma amylase, plasma lipase activity, histological scores) at 1800 or 4200 mg/kg i.v. At the extremely high dose of 1500 mg/kg i.v. plasma amylase and lipase levels were decreased. In lipopolysaccharide-mediated ARDS, AAG was tested at 50, 200 or 600 mg/kg i.v. AAG, but also the placebo formulation decreased the myeloperoxidase content in the bronchoalveolar lavage fluid. Histological alterations were improved by AAG, however, not by the placebo formulation. Lung water content was not significantly influenced by AAG, whereas Evans blue extravasation was significantly diminished by all three doses of AAG. It is concluded that the edematous pancreatitis is the first in vivo condition with increased extravascular fluid accumulation, in which AAG is not effective. Based on data presented here and literature data, there is evidence for a beneficial effect of AAG in acute lung injury.

Topics: Acute Disease; Animals; Bronchoalveolar Lavage Fluid; Ceruletide; Edema; Glycodeoxycholic Acid; Hemorrhage; Lipopolysaccharides; Lung Diseases; Male; Orosomucoid; Pancreatitis; Rats; Rats, Sprague-Dawley; Respiratory Tract Diseases

Acute edematous pancreatitis was induced in cats by perfusing activated pancreatic enzymes through their pancreatic ducts. The ducts had been made permeable to large molecules by one of two techniques. The cats either received ethanol (2 ml/kg every 8 h) and aspirin (25 mg/kg every 8 h) orally for 48 h or had their pancreatic ducts perfused for 1 h with 7.5 mM glycodeoxycholate. When the same procedure was followed, but using 16,16-dimethyl prostaglandin E2 (dmPGE2) (2 micrograms/kg X h infused intravenously for 1 h before and during ductal perfusion with activated enzymes), hemorrhagic pancreatitis developed instead. To investigate whether an increase in pancreatic blood flow or microvascular permeability (both caused by dmPGE2) was important in this phenomenon, we tested the effects of isoproterenol (which increased blood flow) and histamine (which increased microvascular permeability) in the model. Thus in similar experiments, either isoproterenol (0.3 micrograms/kg . min) or histamine phosphate (2 micrograms/kg . min) was infused instead of dmPGE2. The animals that received histamine also developed hemorrhagic pancreatitis. Those that received isoproterenol did not. These observations suggested that an increase in microvascular permeability in the pancreas converted edematous pancreatitis to hemorrhagic pancreatitis. These findings suggest also that clinical studies using prostaglandins to treat patients with pancreatitis should be approached with caution.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Aspirin; Capillary Permeability; Cats; Ethanol; Glycodeoxycholic Acid; Hemorrhage; Histamine; Isoproterenol; Pancreas; Pancreatic Juice; Pancreatitis; Prostaglandins E, Synthetic; Regional Blood Flow