A C Najenson1, A P Courreges1, J C Perazzo2, M F Rubio3, M S Vatta4, L G Bianciotti1,5. 1. Instituto de Inmunología, Genética y Metabolismo (INIGEM-CONICET-UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. 2. Instituto de Patología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 3. Instituto de Investigaciones Médicas (IDIM-CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 4. Cátedra de Fisiología-Instituto de Química y Metabolismo del Fármaco (IQUIMEFA-CONICET-UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. 5. Departamento de Ciencias Biológicas, Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Abstract
AIM: We previously reported that atrial natriuretic peptide (ANP) reduces serum amylase and intrapancreatic trypsinogen activation in the onset of acute pancreatitis whereas secretin increases them. In the present work, we sought to establish the effect of ANP and secretin on the inflammatory response and cell death in experimental acute pancreatitis. METHODS: The expression and activity of key inflammatory mediators and apoptosis were evaluated in the presence or absence of the atrial peptide, secretin or both in cerulein-induced acute pancreatitis in rats. Also, ultrastructural changes in pancreatic acinar cells were assessed by transmission electron microscopy. RESULTS: ANP significantly reduced NF-κB activation and TNF-α intrapancreatic levels. Furthermore, it decreased inducible nitric oxide synthase and cyclooxygenase 2 expression and activity while it diminished myeloperoxidase activity. ANP also stimulated apoptosis as shown by caspase-3 expression and activation as well as TUNEL assay. These findings correlated well with the ultrastructural changes observed in the exocrine pancreas. Although secretin reduced various inflammatory markers, it also diminished caspase-3 activation and the overall response was the aggravation of the disease as reflected by the ultrastructural alterations of pancreatic acinar cells. In the presence of ANP, various effects evoked by secretin were antagonized. CONCLUSION: Present findings show that ANP significantly attenuated the severity of acute pancreatitis in the rat by inducing apoptosis and reducing the inflammatory response and further suggest that ANP may have eventual therapeutic implications in the disease and/or in medical interventions at risk of its developing like endoscopic retrograde cholangiopancreatography.
AIM: We previously reported that atrial natriuretic peptide (ANP) reduces serum amylase and intrapancreatic trypsinogen activation in the onset of acute pancreatitis whereas secretin increases them. In the present work, we sought to establish the effect of ANP and secretin on the inflammatory response and cell death in experimental acute pancreatitis. METHODS: The expression and activity of key inflammatory mediators and apoptosis were evaluated in the presence or absence of the atrial peptide, secretin or both in cerulein-induced acute pancreatitis in rats. Also, ultrastructural changes in pancreatic acinar cells were assessed by transmission electron microscopy. RESULTS: ANP significantly reduced NF-κB activation and TNF-α intrapancreatic levels. Furthermore, it decreased inducible nitric oxide synthase and cyclooxygenase 2 expression and activity while it diminished myeloperoxidase activity. ANP also stimulated apoptosis as shown by caspase-3 expression and activation as well as TUNEL assay. These findings correlated well with the ultrastructural changes observed in the exocrine pancreas. Although secretin reduced various inflammatory markers, it also diminished caspase-3 activation and the overall response was the aggravation of the disease as reflected by the ultrastructural alterations of pancreatic acinar cells. In the presence of ANP, various effects evoked by secretin were antagonized. CONCLUSION: Present findings show that ANP significantly attenuated the severity of acute pancreatitis in the rat by inducing apoptosis and reducing the inflammatory response and further suggest that ANP may have eventual therapeutic implications in the disease and/or in medical interventions at risk of its developing like endoscopic retrograde cholangiopancreatography.
Authors: Ana C Najenson; Mariana Bianchi; Ana P Courreges; Myrian R Rodriguez; Víctor H Casco; Marcelo S Vatta; Liliana G Bianciotti Journal: Pflugers Arch Date: 2019-01-08 Impact factor: 3.657
Authors: Elizabeth O Harrington; Ashok Kumar; Verida Leandre; Zachary S Wilson; Brianna Guarino; Julie Braza; Craig T Lefort; James R Klinger Journal: Am J Physiol Lung Cell Mol Physiol Date: 2022-08-09 Impact factor: 6.011
Authors: Iuliia Polina; Mark Domondon; Rebecca Fox; Anastasia V Sudarikova; Miguel Troncoso; Valeriia Y Vasileva; Yuliia Kashyrina; Monika Beck Gooz; Ryan S Schibalski; Kristine Y DeLeon-Pennell; Wayne R Fitzgibbon; Daria V Ilatovskaya Journal: Am J Physiol Renal Physiol Date: 2020-05-28