Evidence for a role of oxygen derived free radicals in the pathogenesis of caerulein induced acute pancreatitis in rats.
The effects of a polyethylene glycol linked oxygen free radical scavenger enzyme, superoxide dismutase (PEG:SOD) on caerulein induced acute pancreatitis (AP) in rats were examined. Pancreas weights and serum amylase concentrations in rats given a three hour continuous intravenous infusion of caerulein (7.5 micrograms/kg/h, n = 18) for induction of AP followed by a three hour infusion of normal saline were significantly raised by approximately 25% (p less than 0.005) and 750% (p less than 0.001), respectively, compared with values obtained in control rats (n = 7) infused for six hours with normal saline alone. A single intraperitoneal injection of either 1 X 10(4) U/kg (n = 6), 2 X 10(4) U/kg (n = 5), or 4 X 10(4) U/kg (n = 5) of PEG:SOD immediately before caerulein infusion did not significantly alter pancreas weights, serum amylase content, or pancreatic histopathology compared with rats given caerulein alone. By contrast, a single intravenous bolus injection of 4 X 10(4) U/kg (n = 9) of PEG:SOD before caerulein treatment significantly reduced serum amylase content by approximately 25% (p less than 0.05) and a continuous six hour intravenous infusion of 4 X 10(4) U/kg/h of PEG:SOD (n = 5) produced significant reductions of approximately 25% (p less than 0.001), 35% (p less than 0.05), and 50% (p less than 0.01) in pancreas weights, serum amylase concentrations, and acinar cell vacuolisation (p less than 0.01), respectively, compared with values in rats given caerulein alone. In studies using bovine serum albumin linked to polyethylene glycol and infused for six hours at protein concentrations identical to high dose PEG:SOD (n = 6), no beneficial effects against caerulein induced AP were observed. These data suggest that (a) oxygen derived free radicals are involved in the early pathogenesis of caerulein induced AP in rats, and (b) the greatly extended circulating half life of polyethylene PEG:SOD ( > 35 hours in rats compared with less than six minutes for native superoxide dismutase) may make this compound more suitable than native superoxide dismutase as a potential therapeutic agent in AP.
Wisner
J
J
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Green
D
D
Ferrell
L
L
Renner
I
I
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D005609:Free Radicals; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011092:Polyethylene Glycols; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D005609:Free Radicals; D011092:Polyethylene Glycols; D002108:Ceruletide; D013482:Superoxide Dismutase; D010100:Oxygen