The Reserpine-Treated Rat as an Experimental Animal Model for Cystic Fibrosis: Abnormal Cl Transport in Pancreatic Acinar Cells

Martínez, Vicente; Am, Martinez

doi:10.1203/00006450-198810000-00002

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…Results of previous studies of chronic reserpine administration to rats show that the abnormalities in the salivary glands, pancreas, and small intestine closely resemble those seen in CF(9‐11). However, the reserpine model causes severe anorexia, with a weight loss of 40% to 60% of body weight(9), contributing a significant confounding variable. Using the chronically catheterized rat model, we developed a reserpine model that does not cause malnutrition, by maintaining the rats on a liquid diet by bolus injection through a gastric catheter (24).…”

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 60%

“…The development of the chronically catheterized rat (8) allowed us to study the effect of pancreatic enzymes on the intestine. In initial experiments, we used the reserpinized rat (a wellknown model for CF), because the drug induces pancreatic insufficiency, with similar alterations in pancreatic secretions to those found in CF(9‐11). The monounsaturated fatty acid, oleic acid, was added to the experiments, becauses it increases intestinal permeability and causes mucosal injury in the developing piglet(12,13).…”

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confidence: 99%

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The Effect of Intestinal Permeability on Pancreatic Enzyme‐Induced Enteropathy in the Rat

Lloyd‐Still,

Uhing,

Arango

et al. 1998

J. pediatr. gastroenterol. nutr.

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Background:Fibrosing colonopathy in cystic fibrosis occurs in children 2 to 7 years old and is associated with excess doses of high and regular strength lipase pancreatic enzymes, given for more than 6 months. A rat model was developed to study the effects of excessive doses of pancreatic enzymes equivalent to those producing fibrosing colonopathy in cystic fibrosis patients.Methods:Five groups of animals were studied after administration of different combinations of pancreatic enzymes, oleic acid, and reserpine.Results:Pancreatic enzymes alone produced minimal damage to the intestine and none to the liver. Excessive doses of pancreatic enzymes in combination with agents that increased intestinal permeability (oleic acid, reserpine) were associated with intestinal eosinophilia and necrosis of the jejunoileal muscle layer and inflammatory nodules in the liver, which increased with duration of insult.Conclusions:Increased intestinal permeability potentiates damage to the intestine caused by excessive pancreatic enzyme dosage. It is a characteristic of cystic fibrosis that may increase vulnerability to fibrosing colonopathy.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 99%

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The Effect of Intestinal Permeability on Pancreatic Enzyme‐Induced Enteropathy in the Rat

Lloyd‐Still,

Uhing,

Arango

et al. 1998

J. pediatr. gastroenterol. nutr.

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Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

Weizman

1996

Digest Dis Sci

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Plasma immunoreactive cationic trypsin (ogen) is elevated in cystic fibrosis during early infancy, before exocrine pancreatic insufficiency is fully developed. The recently developed cystic fibrosis mouse model carrying a mutated gene presents only minor pathologic findings in the pancreas. However, the reserpinized rat model shows cystic fibrosis-like defects in various exocrine glands, including the exocrine pancreas. Plasma immunoreactive cationic trypsin (ogen) has not been studied yet in this model. The present study explored the plasma immunoreactive cationic trypsin (ogen) pattern and possible mechanisms in this rat model. Plasma immunoreactive cationic trypsin (ogen) (RIA), pancreatic juice volume, protein, and trypsin, and pancreas weight were determined in rats treated with reserpine (0.5 mg/kg/day subcutaneously) for four or seven days, following cerulein stimulation (5 micrograms/kg/dose intraperitoneally), versus pair-fed controls. The first of four consecutive 30 min periods revealed peak values in all parameters. Four-day reserpine-treated rats demonstrated significantly higher plasma immunoreactive cationic trypsin (ogen) levels (167.3 +/- 12.8 vs 88.9 +/- 6.1 ng/ml; P < 0.0001) with similar values of pancreatic juice trypsin (8.2 +/- 2.4 vs 6.6 +/- 1.8 units/mg protein; P = NS) and volume (5.6 +/- 1.3 vs 4.2 +/- 1.6 mg/min/g pancreas; P = NS), compared to controls. Rats treated with reserpine for seven days revealed significantly lower values of plasma immunoreactive cationic trypsin (ogen) (39.2 +/- 8.4 vs 66.8 +/- 4.9 ng/ml; P < 0.001), pancreatic juice trypsin (1.9 +/- 0.3 vs 3.2 +/- 0.9 units/mg protein; P < 0.001) and volume (1.6 +/- 0.7 vs 3.1 +/- 0.6 mg/min/g pancreas; P < 0.001) compared to controls. We conclude that the reserpinized rat model resembles human cystic fibrosis as to elevated plasma immunoreactive cationic trypsin (ogen) before exocrine pancreatic insufficiency is fully developed. Since exocrine pancreatic volume secretion is intact at this stage, the mechanism of elevated plasma immunoreactive cationic trypsin is probably not due to ductular obstruction. We suggest that this model be studied further in order to investigate other possible mechanisms.

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Molecular and cellular biology of cystic fibrosis

McPherson

Dormer

1991

Molecular Aspects of Medicine

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The Reserpine-Treated Rat as an Experimental Animal Model for Cystic Fibrosis: Abnormal Cl Transport in Pancreatic Acinar Cells

Cited by 4 publications

References 18 publications

The Effect of Intestinal Permeability on Pancreatic Enzyme‐Induced Enteropathy in the Rat

The Effect of Intestinal Permeability on Pancreatic Enzyme‐Induced Enteropathy in the Rat

Plasma immunoreactive cationic trypsin(ogen) pattern in reserpinized rat model of cystic fibrosis

Molecular and cellular biology of cystic fibrosis

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