The influence of ethanol on long-term effects of dibutyltin dichloride (DBTC) in pancreas and liver of rats.
The present study was done to determine the additional influence of daily ethanol intake (15% in drinking water ad libitum) on long-term toxic effects of a single administration of dibutyltin dichloride (DBTC, 8 mg/kg b.w. i.v.) in pancreas and liver of rats. Pathohistological changes in pancreas, bile duct and liver as well as pathobiochemical parameters of pancreatitis (amylase and lipase activity), liver lesions (alkaline phosphatase activity and bilirubin) and fibrosis (hydroxyproline and hyaluronic acid) were measured 1 day and 1 to 24 weeks after DBTC- and DBTC/ethanol administration. DBTC alone induced in rats an acute interstitial pancreatitis as well as acute bile duct and liver lesions in the early experimental phase. Later on, the acute inflammatory processes in pancreas and liver took a chronic course resulting in pancreatic fibrosis and liver cirrhosis. Ethanol increased the toxic effects of DBTC on pancreas and liver during the acute and chronic course. In the acute phase lasting 1 day to 2 weeks, ethanol enhanced the DBTC toxicity on acinar cell and bilio-pancreatic duct epithelium as well as the formation of obstructive ductal plugs by necrotic cell debris. The obstruction and cholestasis in the DBTC/ethanol-group were significantly stronger as in the DBTC-group. The significant increase of hydroxyproline in urine and hyaluronic acid in serum of the DBTC/ethanol treated rats after 12 to 24 weeks was connected with a more severe chronic inflammatory fibrosis in pancreas and liver in comparison to the DBTC-treated group.
Merkord
J
J
Institute of Pharmacology and Toxicology, University of Rostock, Germany.
Weber
H
H
Jonas
L
L
Nizze
H
H
Hennighausen
G
G
D000284:Administration, Oral; D000681:Amylases / Q000097:blood; D000818:Animals; D004357:Drug Synergism; D004487:Edema; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D005355:Fibrosis; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000097:blood / Q000652:urine; D007275:Injections, Intravenous; D008049:Lipase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D009336:Necrosis; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced; D051381:Rats; D011917:Rats, Inbred Lew; D012997:Solvents / Q000494:pharmacology
D009947:Organotin Compounds; D012997:Solvents; D000431:Ethanol; D006820:Hyaluronic Acid; D008049:Lipase; D000681:Amylases; C020735:dibutyldichlorotin; D006909:Hydroxyproline