title: Apoptosis of acinar cells is involved in chronic pancreatitis in Wbn/Kob rats: role of glucocorticoids.
abstract: The involvement of pancreatic acinar cell apoptosis and its relation to glucocorticoid exposure were investigated in spontaneously occurring chronic pancreatitis in male Wistar Bonn/Kobori (WBN/Kob) rats. Although most lobules were not inflamed in 10-week-old WBN/Kob, increased apoptosis of pancreatic acinar cells, confirmed by TUNEL staining was focally observed (0.10 +/- 0.10 vs. 0.05 +/- 0.10/field in 10-week Wistar rats). Localized hemorrhagic lesions and brown foci in the splenic lobes were apparent, with significant decrease in pancreas weight in 20-week WBN/Kob rats along with marked apoptosis (1.95 +/- 0.31 vs. 0.07 +/- 0.04/field in 20-week Wistar rats). Electron microscopy revealed apoptotic bodies to be present in acinar cells. Pancreatic myeloperoxidase activities, indirect indices of granulocyte infiltration, as well as histologic scores were significantly increased at 15 and 20 weeks, and endogenous corticosterone levels were significantly decreased at 10, 15, and 20 weeks as compared with values for age-matched Wistar rats. Prednisolone in the drinking water (0.01 mg/mL; calculated dose, 1.03 0.03 mg/kg/d) for 10 weeks significantly attenuated increases in numbers of apoptotic acinar cells and pancreatic myeloperoxidase activities and tended to reduce the histologic scores in 20-week WBN/Kob rats as compared with the vehicle group. In summary, (a) apoptosis of pancreatic acinar cells is involved in chronic pancreatitis, (b) endogenous corticosterone is decreased, and (c) prednisolone treatment attenuates both apoptosis of pancreatic acinar cells and chronic pancreatitis in male WBN/Kob rats. We conclude that apoptosis of acinar cells related to decreased corticosterone may be a trigger of chronic pancreatitis in this model.
authors.affiliation: First Department of Internal Medicine, Nagoya City University, Medical School, Nagoya, Japan. hassy@med.nagoya-cu.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Yokoi
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: H
authors.initials: H
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: H
authors.initials: H
authors.lastname: Ohara
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: T
authors.initials: T
authors.lastname: Joh
authors.forename: M
authors.initials: M
authors.lastname: Itoh
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002467:Cell Nucleus / Q000473:pathology; D002908:Chronic Disease; D004396:Coloring Agents; D003345:Corticosterone / Q000097:blood; D005938:Glucocorticoids / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000188:drug therapy / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D004396:Coloring Agents; D005938:Glucocorticoids; D007328:Insulin; D000324:Adrenocorticotropic Hormone; D011239:Prednisolone; D009195:Peroxidase; D003345:Corticosterone