Oxygen radical generation and acute pancreatitis: effects of dibutyltin dichloride/ethanol and ethanol on rat pancreas.
Recent studies suggest that enhanced release of free oxygen radicals plays an important role in the pathogenesis of acute pancreatitis. Therefore, we studied the activity of the oxygen radical generating xanthine oxidase (XOD) in pancreatic tissue from rats treated with either dibutyltin dichloride/ethanol (DBTC/EtOH: 6 mg kg-1/13.7 mg kg-1, i.v.), ethanol alone (EtOH: 13.7 mmol kg-1, i.v.), or isotonic saline (NaCl) as control. We also investigated activities of the oxygen radical scavengers superoxide dismutase (SOD) and glutathione peroxidase (GPX). In addition, levels of the lipid peroxidation marker malondialdehyde (MDA) were determined. Enhanced activity of XOD was not detected. While SOD activity 1 and 6 h after treatment was significantly more reduced by DBTC/EtOH than by EtOH alone, no difference was found thereafter. Correspondingly, both regimens diminished GPX activity. Moreover, DBTC/EtOH and EtOH rapidly increased MDA levels within 1 h, indicating release of oxygen radicals early on after administration. After 16 h the MDA concentration was still elevated only in the DBTC/EtOH group. Although similar metabolic alterations were observed in both groups, only DBTC/EtOH induced acute interstitial pancreatitis within 24 h. We conclude that (a) a tissue imbalance between oxidants and antioxidants might be of importance in the pathogenesis of DBTC/EtOH-induced acute interstitial pancreatitis; (b) although EtOH increases oxygen radical levels, additional damage is required for development of acute pancreatitis; (c) XOD does not seem to be responsible for significant oxygen radical generation; and (d) the DBTC/EtOH model is a useful tool to study acute interstitial pancreatitis in rats.
Institute of Clinical Chemistry and Pathobiochemistry, University of Rostock, Germany.
H
H
Weber
J
J
Merkord
L
L
Jonas
A
A
Wagner
H
H
Schröder
U
U
Käding
A
A
Werner
W
W
Dummler
D000208:Acute Disease; D000818:Animals; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005609:Free Radicals; D008049:Lipase / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D009947:Organotin Compounds / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010195:Pancreatitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000502:physiology
D005609:Free Radicals; D009947:Organotin Compounds; D000431:Ethanol; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D008049:Lipase; C020735:dibutyldichlorotin; D010100:Oxygen