Relaxin prevents the development of severe acute pancreatitis.
OBJECTIVE
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-inflammatory 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 time-points. 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 efficiency of relaxin.


CONCLUSIONS
Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.
Cosen-Binker
Laura Iris
LI
RHC-LICB Medical Research Institute-Buenos Aires, Argentina. laura.cosen.binker@utoronto.ca
Binker
Marcelo Gustavo
MG
Cosen
Rodica
R
Negri
Gustavo
G
Tiscornia
Osvaldo
O
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001798:Blood Proteins / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D020169:Caspases / Q000502:physiology; D004195:Disease Models, Animal; D007249:Inflammation; D008168:Lung / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010179:Pancreas / Q000098:blood supply / Q000503:physiopathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000502:physiology; D012065:Relaxin / Q000494:pharmacology* / Q000502:physiology; D015398:Signal Transduction; D014664:Vasodilation
D001798:Blood Proteins; D011965:Receptors, Glucocorticoid; D009569:Nitric Oxide; D012065:Relaxin; D002097:C-Reactive Protein; D020169:Caspases