Experimental Pancreatitis Induced by Synthetic Prooxidant Tert-butyl Hydroperoxide

Abstract

The purpose of this study was to verify whether injection of tert-butyl hydroperoxide (Bu(t)OOH, a well-known prooxidant agent) into the bile-pancreatic duct can induce acute pancreatitis. A rapid blockade of the secretion was observed in the majority of the animals after 3 hours of observation. After 6 hours, the secretion reached a very low level, significantly different compared with controls. In groups of rats injected with Bu(t)OOH, pancreatic weight gain was observed compared with the rats injected with physiologic saline. Histology of pancreata removed 3 hours after injection of Bu(t)OOH showed acinar cell vacuolization, interstitial edema, focal necrosis of pancreatic acini, fat-tissue necrosis, and leukocyte infiltration of the organ. These changes were considerably greater after the 6-hour observation period. Electron-microscopic inspection revealed profound morphologic changes 3 hours after Bu(t)OOH injection. The control rats receiving physiologic saline alone had well-preserved pancreatic tissue structure. In conclusion, injection of the prooxidant agent, tert-butyl hydroperoxide, into common bile-pancreatic duct induces acute necrotizing pancreatitis, which indicates the crucial role of free radical reactions in pathogenesis of this disease.

Enzymatic and histological alterations in the isolated perfused rat pancreas under conditions of oxidative stress

“…The use of tert-butylhydroperoxide as a free radical source is very well established in experimental hepatology [45]. The synthetic tert-butylhydroperoxide decreased the exocrine pancreatic secretion in animal experiments and induced an acute necrotic pancreatitis after intraductal administration [46,47].…”

Basic Experimental Pancreatitis Models for Beginners

“…These have included stimulating factors and toxic substances such as bile acids (taurocholate or glycodeoxycholic acid), ethyl alcohol, peracetate and tert-butyl hydroperoxide. The most common of all these substances are bile acids [76][77][78].…”

Towards a Novel Treatment Strategy for Acute Pancreatitis

“…The direct delivery of potent oxidants via close arterial injection [197, 214, 215]or intraductally [216]produces pancreastasis and pancreatitis more predictably than when indirect methods are used to produce oxidative stress [213, 217, 218]. …”