Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions.
Dibutyltin dichloride (DBTC; 6 mg/kg body weight, i.v.) induced acute interstitial pancreatitis in rats. The course of the pancreatitis was examined within 28 days by light and electron microscopy as well as by pathobiochemistry (amylase, lipase, alkaline phosphatase, and bilirubin in serum; tin concentration in biliopancreatic juice, tissue, and concretions). The pathogenesis of the DBTC-induced pancreatitis in rats was studied by different experimental designs (in intact animals, after bile duct ligation, after surgical bypass of the bile duct). DBTC caused toxic necrosis of the biliopancreatic duct epithelium, which is then shed into the duct and forms obstructing plugs in the distal common bile duct. Interstitial pancreatitis occurred during the first 4 days, accompanied by significantly increased activities of serum alpha-amylase and lipase. After 7 days extensive infiltration of the pancreatic interstitium with mononuclear cells was observed. Twenty-eight days after administration of DBTC one-third of the rats showed periductal and interstitial fibrosis as well as an active inflammatory process in the pancreas. The findings suggest a twofold pathogenesis of the DBTC-induced pancreatitis: first, the cytotoxic effects on the biliopancreatic duct epithelium lead to epithelial necrosis with obstruction of the duct, subsequent cholestasis, and interstitial pancreatitis; and second, the hematogenic DBTC effects cause direct injury of pancreatic cells (mitochondrial damage, autophagy, cell necrosis) followed by interstitial edema and inflammation. Both processes lead to this special type of DBTC-induced acute pancreatitis with a tendency to a chronic course, when the obstruction of the duct and cholestasis persist.
Merkord
J
J
Institute of Pharmacology, University of Rostock, Germany.
Jonas
L
L
Weber
H
H
Kröning
G
G
Nizze
H
H
Hennighausen
G
G
D000208:Acute Disease; D000818:Animals; D001652:Bile Ducts / Q000473:pathology / Q000601:surgery; D005355:Fibrosis; D008026:Ligation; D008049:Lipase / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D009947:Organotin Compounds / Q000032:analysis / Q000633:toxicity*; D010179:Pancreas / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D010183:Pancreatic Ducts / Q000473:pathology / Q000648:ultrastructure; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D000516:alpha-Amylases / Q000097:blood
D009947:Organotin Compounds; D008049:Lipase; D000516:alpha-Amylases; C020735:dibutyldichlorotin