Changes in rat and mouse salivary glands and pancreas after chronic treatment with diuretics: a potential animal model for cystic fibrosis.
Defective transepithelial chloride and water transport is thought to be the cellular basis of the disease cystic fibrosis (CF). Therefore, it was attempted to develop an animal model for this disease by chronically inhibiting transepithelial chloride transport in experimental animals by long term treatment with high doses of diuretics. In the present study, changes in the salivary glands and pancreas after such treatment were investigated by X-ray microanalysis and electron microscopy. Treatment of rats for one month with diuretics caused a significant decrease in chloride and an increase in calcium in the acinar cells of the submandibular gland. This increase was due to accumulation of mucus in the cells. The strongest effect was obtained after combined treatment with furosemide and acetazolamide. Only minor changes were noted in the parotid gland and the pancreas. Treatment of mice for three months with diuretics caused similar changes in the submandibular glands. In addition, marked changes in the pancreas were observed. The chloride content of the pancreatic acinar cells was decreased. In many acinar cells, only very few zymogen granules were present. The morphological and microanalytical results point to severe dysfunction of the exocrine pancreas. These changes parallel those found in patients with CF, and the chronically furosemide-treated mouse thus could serve as an animal model for this disease.
Sagström
S
S
Department of Human Anatomy, University of Uppsala, Sweden.
McMillan
E B
EB
Marijianowski
M
M
Mulders
H
H
Roomans
G M
GM
D000086:Acetazolamide / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000493:pharmacokinetics; D003550:Cystic Fibrosis / Q000473:pathology; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D011188:Potassium / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012469:Salivary Glands / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D012964:Sodium / Q000493:pharmacokinetics
D002712:Chlorides; D004232:Diuretics; D004338:Drug Combinations; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D000086:Acetazolamide; D011188:Potassium