Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the mouse.

Abstract

Studies in animal models suggest that oxygen radicals may be important in the pathogenesis of acute pancreatitis. Because glutathione is an essential component of the defense against radical-mediated cellular injury, we investigated whether pancreatic glutathione content is influenced by inducing acute pancreatitis and whether augmenting the intracellular supply of glutathione would alter the course of pancreatitis. Caerulein, a decapeptide cholecystokinin analogue, induces acute necrotizing pancreatitis in mice when given in high doses (50 ,ag/kg per h) over a period of 6 h. The pancreatic glutathione content (total, GSH + GSSG) in mice treated with high-dose caerulein fell to 17% of normal within 4 h of beginning caerulein and recovered toward normal after discontinuing caerulein treatment. Mice treated with glutathione monoethyl ester (20 mmol/kg 1 h before caerulein, 10 mmol/kg 3 and 7 h after starting caerulein) were found to have blunted depletion of pancreatic glutathione, diminished histologic evidence ofpancreatitis (necrosis, inflammation, and vacuolization), and lower serum amylase values compared with mice treated with caerulein alone. These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation ofthe pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis. (J. Clin. Invest. 1992.

Reactive oxygen species inactivation improves pancreatic capillary blood flow in caerulein-induced pancreatitis in rats

“…Also the serum amylase increase in group 2 was statistically reduced in the presence of the PBN. These findings are in accord with reports of gluthatione depletion 25 , decrease of superoxide dismutase activity in the pancreatic tissue and elevation malondialdehyde concentration 26 (a by-product of lipid peroxidation) seen during caerulein-induced pancreatitis. During the effort to produce and secret pancreatic enzymes by caerulein hyperstimulation, a disturb in the oxidantantioxidant balance may occur in the pancreatic cell.…”

Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis

“…Although certain amounts of ROS are produced under physiological conditions, they are believed to be captured by a sufficient amount of antioxidants; however, during the development of AP, the increased production of ROS is thought to overwhelm the antioxidant defenses (46). Indeed, a depletion of pancreatic SOD and glutathione content, possibly because of their exhaustion, occurs in mice with CER-induced AP (12,31). Thus endogenous antioxidants may have a critical role in preventing the progression of pancreatitis (31).…”

“…Indeed, a depletion of pancreatic SOD and glutathione content, possibly because of their exhaustion, occurs in mice with CER-induced AP (12,31). Thus endogenous antioxidants may have a critical role in preventing the progression of pancreatitis (31). To evaluate the protective role of TRX-1 against such oxidative tissue injury, we measured the MDA concentration, a marker of lipid peroxidation, in the pancreas of mice with AP.…”

Chronic Ethanol Administration Induces Oxidative Alterations and Functional Impairment of Pancreatic Mitochondria in the Rat

“…Acute pancreatic injury following exposure to toxic agents is reported to be characterized by a decrease in the GSH concentration and enhancement of lipid peroxidation [24]. Moreover, when diethylmaleate, a GSH depletor, is given before ETOH, the oxidative damage to lipids and proteins were exaggerated [9].…”