Repeated administration of a mild acute toxic dose of di-n-butyltin dichloride at intervals of 3 weeks induces severe lesions in pancreas and liver of rats.
Di-n-butyltin dichloride (DBTC) induced thymus atrophy, bile duct lesions, pancreatitis, and liver lesions in rats. Depending on dose [6 and 8 mg/kg intravenous (i.v.) DBTC] and time (1-24 weeks), the lesions in pancreas developed to a pancreatic fibrosis and the lesions in liver to liver cirrhosis. A single i.v. administration of 4 mg/kg DBTC induces a mild interstitial pancreatitis after 2-4 days followed by a restitutio ad integrum after 21-28 days. In the present study, the lesions of biliopancreatic duct, pancreas, and liver of rats after repeated administration of 4 mg/kg DBTC i.v. at intervals of 3 weeks have been investigated. The histopathological changes of pancreas and liver were examined by light microscopy 1,4, and 7 days and 2,3,4,6,9, and 12 weeks after administration of DBTC. Furthermore, pathobiochemical parameters of pancreatitis (amylase and lipase activity in serum), liver lesions (alkaline phosphatase activity and bilirubin in serum), and of fibrosis (hyaluronic acid in serum) were studied. Repeated administration of rats with DBTC (4 mg/kg i.v.) at intervals of 3 weeks induced an acute interstitial pancreatitis and after 9-12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia, inflammation in periportal tract, and necrosis). In serum, elevated levels of alkaline phosphatase, bilirubin, and hyaluronic acid were found. This study demonstrates that the organotin compound induces toxic effects on pancreas and liver of rats by repeated administration of lower doses at long intervals. The risk of exposure to organotin at long intervals should be considered.
Merkord
J
J
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Rostock, Germany.
Weber
H
H
Kröning
G
G
Hennighausen
G
G
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D001663:Bilirubin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D006820:Hyaluronic Acid / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D008049:Lipase / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D010183:Pancreatic Ducts / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000737:chemistry / Q000187:drug effects; D013997:Time Factors; D014001:Tin / Q000032:analysis
D007166:Immunosuppressive Agents; D009947:Organotin Compounds; D014001:Tin; D006820:Hyaluronic Acid; D008049:Lipase; D000469:Alkaline Phosphatase; C020735:dibutyldichlorotin; D001663:Bilirubin