Materials and Methods

To investigate the mechanism of fibrosis progression in chronic pancreatitis, we studied the process of pancreatic fibrosis in male dogs (approximately 12 kg body weight) after oral administration of DL-ethionine (ethionine) as methionine analogue.

Group 1: Ethionine at a dose of 130mg/kg/day was given orally for 7 days. Dogs were sacrificed 1, 2, 3, 7 and 30 days after the last feeding.

Group 2: Ethionine at doses of 10, 50 and 100mg/kg was given once or twice a week for 10 or 20 weeks. Dogs were sacrificed 7 days after the last feeding.

Group 3: Ethionine at a dose of 75 mg/kg was given once a week for 15 weeks. Dogs were sacrificed 2, 3, 4 and 26 weeks after the last feeding.

Pancreas tissues were fixed in glutaraldehyde (2%) phosphate buffer (0.1 m, pH 7.4) at 4°C for 2 h and subjected to electron microscopic analysis. Other pancreas tissues were frozen for immunohistochemistry and fixed in formaldehyde (10%) for histochemistry and immunohistochemistry.

Fig. 1. Group 1. Day 3. Mild proliferation of spindle shaped cells in the periacinar area. Degeneration with decreased number of zymogen granules in acinar cells.

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