Relaxin prevents the development of severe acute pancreatitis

Abstract

AIM:To investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischemia-reperfusion injury. Microvascular integrity and inhibition of pro-infl ammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS:AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS:Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the effi ciency of relaxin. CONCLUSION:Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist

VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis

“…Pancreatic and lung tissue were graded on a scale of 0-4 each for edema, hemorrhage, leukocyte infiltration, and necrosis, as previously described (8,24,25). Histologic changes were graded in a blinded manner by 2 independent observers counting the frequency of foci per field seen at ×40 (0, absent; 1, mild; 2, moderate; 3, severe; 4, overwhelming).…”

“…In WT and Vamp8 -/-mice, ED plus saline treatment induced very mild edema and leukocyte infiltration of the pancreatic tissues that were more prominent in the WT group. When these ED-fed groups were treated with Cch, the WT group developed moderate to severe pancreatitis characterized by parenchymal edema, necrosis with abundant leukocyte infiltration, fat necrosis, congested blood vessels within the peripancreatic fat, and hemorrhage (24,25). Although all of these histologic changes of pancreatitis were also present in the Vamp8 -/-mice, these features were much milder in the Vamp8 -/-group.…”

“…Cch injections) was used to block the development of pancreatitis. Figure 1 shows the representative histology, and Table 1 quantifies the pancreatic damage (24,25). In WT and Vamp8 -/-mice, ED plus saline treatment induced very mild edema and leukocyte infiltration of the pancreatic tissues that were more prominent in the WT group.…”

Metabolomics reveals critical adrenergic regulatory checkpoints in glycolysis and pentose–phosphate pathways in embryonic heart

“…All samples were centrifuged at 6000g for 5 min at 4°C. Supernatant was collected and neutralized with 1X Tris-acetate, as described previously (12,69). ATP measurements were performed with the ATPlite Bioluminescence Assay (Perkin Elmer) according to the manufacturer's protocol.…”

Mitochondrial dysfunction and apoptosis of acinar cells in chronic pancreatitis

“…TCA in the supernatant was neutralized and diluted to a fi nal concentration of 0.1% with Tris-acetate buffer (pH 7.75). [27][28][29] ATP was measured in tissue lysate with a commercially available luciferin-luciferase bioluminescence kit (Promega Enliten, Madison, WI, USA) according to the manufacturer's instructions. The readings were taken using a 10-s integration period with a monolight luminometer.…”