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Influence of Hydrocortisone, Prednisolone, and NO Association on the Evolution of Acute Pancreatitis

Digestive Diseases and Sciences volume 51, pages 915–925 (2006)Cite this article

Abstract

Leukocyte activation, inflammatory up-regulation, and microcirculatory disruption associated with ischemia-reperfusion injury are hallmarks in the pathogenesis of acute pancreatitis (AP). NO donors ensure microvascular integrity, while glucocorticoids act as anti-inflammatory and immune modulator drugs. AP was induced by the biliopancreatic duct outlet exclusion-closed duodenal loops (BPDOE-CDLs) model. Treatment with hydrocortisone (6 mg/kg) or prednisolone (0.5 mg/kg) alone or together with DETA-NO (0.5 mg/kg) was done (a)1 hr pre or (b)1 hr post, or (c) 1 hr pre and 4 hr post ,or (d) 4 hr post triggering AP. NOS inhibition by l-NAME (15 mg/kg) and glucocorticoid receptor blockage by mifepristone (3 mg/kg) was considered. AP severity was assessed by biochemical and histopathological analyses. Treatment with glucocorticoids together with DETA-NO 1 hr pre and 4 hr post BPDOE-CDLs reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage, and neutrophil infiltrate were also decreased. Hydrocortisone together with DETA-NO rendered the best results. We conclude that AP severity was significantly diminished by glucocorticoids associated with DETA-NO, with the optimal dose and time point of administration being crucial to provide adequate protection against AP.

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Acknowledgments

This paper is dedicated to the memory of Julio Nestor Cosen, MD, PhD, a devoted gastroenterologist. We gratefully acknowledge Delia Garrido, PhD, for her technical assistance with statistics and Andras Kapus, MD, PhD, and Sergio Grinstein, PhD, for their ongoing support and valuable scientific teachings and advice.

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Affiliations

  1. Programa de Estudios Pancreáticos, Hospital de ClínicasDepartamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Laura Iris Cosen-Binker, Marcelo Gustavo Binker & Osvaldo Tiscornia

  2. Cátedra de Gastroenterología y Enzimología Clínica, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    Laura Iris Cosen-Binker & Gustavo Negri

  3. RHC-LICB Medical Research Laboratory, Buenos Aires, Argentina

    Laura Iris Cosen-Binker, Marcelo Gustavo Binker & Rodica Cosen

  4. Critical Care Program, Organ Injury Research, Surgery Department, Saint Michael’s Hospital, Toronto, Canada

    Laura Iris Cosen-Binker

  5. Program of Cell Biology, The Hospital for Sick Children, Toronto, Canada

    Marcelo Gustavo Binker

  6. Saint Michael’s Hospital, Critical Care Program, Organ Injury Research, Surgery Department, 30, Bond Street, Room 9-014, Toronto, Ontario, M5B 1W8, Canada

    Laura Iris Cosen-Binker

Authors
  1. Laura Iris Cosen-Binker
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  2. Marcelo Gustavo Binker
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  3. Rodica Cosen
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  4. Gustavo Negri
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  5. Osvaldo Tiscornia
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Correspondence to Laura Iris Cosen-Binker.

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This work was supported by a research grant to Dr. Laura Iris Cosen-Binker from GlaxoSmithKline S.A.

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Cosen-Binker, L.I., Binker, M.G., Cosen, R. et al. Influence of Hydrocortisone, Prednisolone, and NO Association on the Evolution of Acute Pancreatitis. Dig Dis Sci 51, 915–925 (2006). https://doi.org/10.1007/s10620-005-9052-6

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Keywords

  • Acute pancreatitis
  • Glucocorticoids
  • Hydrocortisone
  • Prednisolone
  • Nitric oxide donors