Therapeutic implications of oxidative stress in acute and chronic pancreatitis

Abstract

A significant advance has been made in the arena of research in chronic, but not acute, pancreatitis. There is now solid evidence to justify the use of oral antioxidants in the treatment of patients with chronic pancreatitis. The progress in clinical research on antioxidants in acute pancreatitis is hampered by several factors, including suboptimal classification of acute pancreatitis and route of administration used in previous studies.

Soluble Epoxide Hydrolase Pharmacological Inhibition Ameliorates Experimental Acute Pancreatitis in Mice

“…Further experiments are warranted to investigate the molecular mechanisms by which apoptotic and necrotic pathways contribute to acinar cell death. It is worth noting that pPERK and the eIF2a target ATF4 can initiate cytoprotective signaling pathways to protect from harmful effects of oxidants of relevance in AP (Petrov, 2010). Although additional studies are required to delineate the precise signaling mechanisms underlying the protective effects of sEH pharmacological inhibition in AP, it is likely that attenuated inflammatory response and ER stress are important contributing factors.…”

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis

“…As a consequence ATF4 acts as a transcription factor to induce genes important in translation, transport, and metabolism of amino acids, secretion, resistance to oxidative stress, and protein degradation (34). As Lu et al (46) describe, pPERK and downstream targets of ATF4 can protect cells from lethal effects of oxidants of relevance in AP. Bardag-Gorce et al describe a unique upregulation of ATF4 in liver tissue induced by the use of proteasome inhibitors (14a).…”

Protective Effects of Lycopene on Cerulein-Induced Experimental Acute Pancreatitis in Rats

“…Many of the systemic features of AP can be attributed to the release of proteolytic enzymes, cytotoxic and inflammatory substances, reactive oxygen species (ROS), cytokines, and other mediators into the circulation and explosive activation of the systemic inflammatory response [3][4][5].…”