Basic Research
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World J Gastroenterol. Mar 14, 2006; 12(10): 1558-1568
Published online Mar 14, 2006. doi: 10.3748/wjg.v12.i10.1558
Relaxin prevents the development of severe acute pancreatitis
Laura Iris Cosen-Binker, Marcelo Gustavo Binker, Rodica Cosen, Gustavo Negri, Osvaldo Tiscornia
Laura Iris Cosen-Binker, Marcelo Gustavo Binker, Rodica Cosen, Marcelo Gustavo Binker, Osvaldo Tiscornia, Gustavo Negri, RHC-LICB Medical Research Institute-Buenos Aires, Argentina Laura Iris Cosen-Binker, Programa de Estudios Pancreáticos-Hospital de Clínicas, Universidad de Buenos Aires, Argentina Laura Iris Cosen-Binker, Cátedra de Gastroenterología y Enzimología Clínica-Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina
Author contributions: All authors contributed equally to the work.
Supported by a research grant given to Dr Laura Iris Cosen-Binker by GlaxoSmithKline S.A.
Correspondence to: Dr. Laura Iris Cosen-Binker, BD. PhD, Saint Michael’s Hospital, Critical Care Program -Organ Injury Research- Surgery Department, 30 Bond Street - Room 9-014, Toronto-Ontario-M5B 1W8, Canada.
Telephone: +1-416-8646060 Fax: +1-416-9259069
Received: September 8, 2005
Revised: September 26, 2005
Accepted: October 9, 2005
Published online: March 14, 2006

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-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.

CONCLUSION: Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.

Keywords: Acute pancreatitis, Relaxin, Nitric oxide, Glucocorticoid receptor, Necrosis, Apoptosis