Oxidative Stress In Acute Pancreatitis Research Articles

Optimising outcomes in acute pancreatitis.

Acute pancreatitis is a common cause for presentation to emergency departments. Common causes in Western societies include biliary pancreatitis and alcohol (the latter in the setting of chronic pancreatitis). Acute pancreatitis also follows endoscopic retrograde pancreatography in 5 to 10% of patients, a group that could potentially benefit from prophylactic treatment. Although episodes of pancreatitis usually run a relatively benign course, up to 20% of patients have more severe disease, and this group has significant morbidity and mortality. Therefore, attempts have been made to identify, at or soon after presentation, those patients likely to have a poor outcome and to channel resources to this group. The mainstay of treatment is aggressive support and monitoring of those patients likely to have a poor outcome. Pharmacotherapy for acute pancreatitis (both prophylactic and in the acute setting) has been generally disappointing. Efforts initially focused on protease inhibitors, of which gabexate shows some promise as a prophylactic agent. Agents that suppress pancreatic secretion have produced disappointing results in human studies. Infection of pancreatic necrosis is associated with high mortality and requires surgical intervention. In view of the seriousness of infected necrosis, the use of prophylactic antibacterials such as carbapenems and quinolones has been advocated in the setting of pancreatic necrosis. Similarly, data are accumulating to support the use of prophylactic antifungal therapy. Recently, it has become apparent that the intense inflammatory response associated with acute pancreatitis is responsible for much of the local and systemic damage. With this realisation, future efforts in pharmacotherapy are likely to focus on suppression or antagonism of pro-inflammatory cytokines and other inflammatory mediators. Similarly, animal studies have demonstrated the importance of oxidative stress in acute pancreatitis, although to date there is a paucity of information regarding the efficacy of antioxidants. Although the clinical course for most patients with acute pancreatitis is mild, severe acute pancreatitis continues to be a clinical challenge, requiring a multidisciplinary approach of physician, intensivist and surgeon.

Acute oxidative stress modulates secretion and repetitive Ca 2+ spiking in rat exocrine pancreas

The effects of the oxidant tert-butylhydroperoxide ( t-buOOH) on carbachol-stimulated pancreatic secretion in the vascularly perfused rat pancreas have been studied in parallel with [Ca 2+] i signalling and amylase output in perifused rat pancreatic acinar cells. Perfusion of the pancreas with t-buOOH (0.1–1 mM) caused a rapid and irreversible inhibition of carbachol-stimulated (3×10 −7 M) amylase and fluid secretion. Pre-perfusion of the pancreas with vitamin C and dithiothreitol or a cocktail of GSH and GSH-precursor amino acids provided only marginal protection against the deleterious effects of t-buOOH, even though GSH levels were elevated significantly. In perifused pancreatic acini, repetitive [Ca 2+] i spikes evoked by carbachol (3×10 −7 M) were sustained for 40 min. t-buOOH (1 mM) acutely increased the amplitude and duration of Ca 2+ spikes, then attenuated Ca 2+ spiking and subsequently caused a marked and sustained rise in [Ca 2+] i. t-buOOH-induced alterations in carbachol-stimulated [Ca 2+] i signalling and amylase release in perifused pancreatic acini were prevented by vitamin C. Although vitamin C restored impaired Ca 2+ signalling and maintained amylase output in pancreatic acini, it seems likely that oxidative stress inhibits fluid secretion irreversibly in the intact pancreas, resulting in a loss of amylase output. Thus, perturbations in [Ca 2+] i signalling may not fully explain the secretory block caused by oxidative stress in acute pancreatitis.

Effect of selenium administration on various laboratory parameters in patients with acute pancreatitis

Recent studies presented evidence that activation of oxygen derived free radicals occurs in patients with acute pancreatitis. The purpose of this study was to evaluate the effect of sodium selenite as a possible antioxidant therapy in acute pancreatitis. 16 patients with moderate form of acute pancreatitis received a high dose of sodium selenite. Selenium in serum and whole blood, zinc, copper, manganese, superoxid dismutase (SOD), glutathione peroxidase (Gpx) and malondialdehyde (MDA) were determined (before selenium substitution, 3 days later, 8 days later, before demission). No selenium deficiency could be detected before selenium substitution. The selenium therapy caused a significant increase in selenium, a moderate increase in activity of Gpx, a significant decrease in activity of MDA, whereas SOD remained unchanged. Concerning the particular point of view of "deficiency management", there is no need of selenium substitution in patients with a moderate form of acute pancreatitis in our region. The highly normal selenium concentration we established by our therapy is possibly connected with a decrease of the oxidative stress in acute pancreatitis. More clinical follow-up studies with more patients, who have different grades of severity of the acute pancreatitis, and besides that a control group of patients without selenium substitution, are necessary for evaluating the clinical relevance of our results.

Transgenic Copper/Zinc-Superoxide Dismutase Ameliorates Caerulein-Induced Pancreatitis in Mice

The role of oxidative stress in acute pancreatitis was investigated by comparing the pathological features of caerulein pancreatitis between transgenic mice that overexpress human Cu/Zn-superoxide dismutase (SOD) and nontransgenic littermates. Both the elevation of serum amylase and the formation of pancreatic edema during the pancreatitis were significantly reduced in the transgenic mice compared with the nontransgenic littermates. In the transgenic mice, the pancreatitis-associated reduction of Cu/Zn-SOD activity in the pancreatic tissues was significantly smaller than that in the nontransgenic mice. These results provide direct evidence that the elevation of intracellular oxygen radicals is an important factor for the progress of acute edematous pancreatitis.