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 p lays an important role in the pathogenesis of acute pancreatitis. Ther efore, we studied the activity of the oxygen radical generating xanthi ne oxidase (XOD) in pancreatic tissue from rats treated with either di butyltin 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 radic al scavengers superoxide dismutase (SOD) and glutathione peroxidase (G PX). In addition, levels of the lipid peroxidation marker malondialdeh yde (MDA) were determined. Enhanced activity of XOD was not detected. While SOD activity 1 and 6 h after treatment was significantly more re duced by DBTC/EtOH than by EtOH alone, no difference was found thereaf ter. Correspondingly, both regimens diminished GPX activity. Moreover, DBTC/EtOH and EtOH rapidly increased MDA levels within 1 h, indicatin g 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 antioxidant s might be of importance in the pathogenesis of DBTC/EtOH-induced acut e interstitial pancreatitis; (b) although EtOH increases oxygen radica l levels, additional damage is required for development of acute pancr eatitis; (c) XOD does not seem to be responsible for significant oxyge n radical generation; and (d) the DBTC/EtOH model is a useful tool to study acute interstitial pancreatitis in rats.