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Pancreatic structure and function in the immature reserpinized rat
Insights
Reserpine treatment in immature rats, mimicking cystic fibrosis, caused pancreatic changes. Prenatal and neonatal exposure induced hypoplasia and abnormal zymogen granules, suggesting a suitable animal model.
Area of Science:
- Pancreatology
- Developmental Biology
- Pharmacology
Background:
- Cystic fibrosis (CF) in infants is associated with pancreatic exocrine insufficiency.
- Current animal models for studying CF-related pancreatic issues in neonates are limited.
- Reserpine is known to affect adult rat pancreas; its effects on immature pancreas are less understood.
Purpose of the Study:
- To evaluate the suitability of reserpine-induced pancreatic changes in immature rats as a model for infant cystic fibrosis.
- To investigate the effects of prenatal and neonatal reserpine administration on pancreatic development and function.
Main Methods:
- Immature rats were administered reserpine during fetal development or as neonates, using lower doses than previously reported to avoid lethality.
- Pancreatic tissue was analyzed at various time points (fetal, 1-day-old, 7-day-old, 14-day-old, 21-day-old) for morphological and biochemical changes.
- Electron microscopy was employed to examine pancreatic acinar cell structure and zymogen granules.
Main Results:
- Prenatal reserpine exposure led to fetal pancreatic hypoplasia with elevated chymotrypsinogen at 1 day, followed by hyperplasia at 7 days.
- Neonatal reserpine exposure resulted in pancreatic hypoplasia and decreased measured parameters at 7 days.
- Electron microscopy revealed acinar cell degeneration, abnormal zymogen granules, and altered granule content/size in treated rats compared to controls.
- Progressive recovery was observed in both groups within 2 weeks post-treatment.
Conclusions:
- Prenatal and neonatal reserpinization in rats induces pancreatic alterations resembling those observed in cystic fibrosis.
- This reserpine-induced model in immature rats shows potential for studying pancreatic exocrine insufficiency in infant cystic fibrosis.
- Further research is warranted to fully characterize this model and its applicability to CF pathogenesis.
Abstract:
Immature rats were reserpinized to determine whether the model used for adults may be suitable for the study of pancreatic exocrine insufficiency seen in infants with cystic fibrosis. Rats were reserpinized by injections either into pregnant dams or into newborn rats. The dose of reserpine used by others was lethal to immature rats, so lower doses were used. Pancreas from 1-day-old fetal-treated pups was hypoplastic, but concentration of chymotrypsinogen was elevated. At age 7 days hyperplasia was seen. When rats were reserpinized as neonates, hypoplasia and decrease in all parameters measured was observed at age 7 days. Progressive recovery occurred during the following 2 weeks in both groups. Electron microscopic study of the fetal-treated 24-hr-old pancreas revealed evidence of acinar cell degeneration with the presence of abnormal zymogen granules. At age 7 days the pancreas from neonatal-treated rat pups appeared to have a reduced number of granules. At ages 14 and 21 days the pancreas was similar to that seen at age 7 days except that the granules were larger and some acinar lumina were filled with a finely granular, homogeneously dense material. It is concluded that prenatal and neonatal reserpinization of rats induces changes in pancreas similar to those found in cystic fibrosis.