Abstract
Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.
Highlights
Acute pancreatitis is an inflammatory pathology characterized by elevation of serum pancreatic enzymes and acute abdominal pain [1]
Digestive enzymes, which are exported outside the cells and lysosomal hydrolases, which are transported into lysosomes, are normally separated from each other while they pass through the Golgi system [2,3]
We show that HT alleviated caerulein induced pancreatitis
Summary
Acute pancreatitis is an inflammatory pathology characterized by elevation of serum pancreatic enzymes and acute abdominal pain [1]. The normal secretion of digestive enzymes is modified during pancreatitis. Digestive enzymes, which are exported outside the cells and lysosomal hydrolases, which are transported into lysosomes, are normally separated from each other while they pass through the Golgi system [2,3]. The separation of digestive enzymes from lysosomal hydrolases is defective and, as a result, both types of enzyme become colocalized within intracellular vacuoles [2]. This colocalization phenomenon may result in premature activation of digestive enzymes. Intestinal dysfunction and secondary inflammatory issues aggravate acute pancreatitis retroactively and are prodromes of systemic complications [9,10]
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