Continuous regional arterial infusion with fluorouracil and octreotide attenuates severe acute pancreatitis in a canine model

PLoS One. 2012;7(5):e37347. doi: 10.1371/journal.pone.0037347. Epub 2012 May 24.

Abstract

Aim: To investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP).

Materials and methods: The animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, α-tumor necrosis factor (TNF-α), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto- prostaglandin F1α were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study.

Results: Pathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-α and amylase activity (P<0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B(2) level increased in SAP, but the ratio of thromboxane B(2)/6-keto- prostaglandin F(1α) decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P<0.05).

Conclusions: The findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amylases / blood
  • Animals
  • Antimetabolites / administration & dosage
  • Antimetabolites / therapeutic use*
  • Creatinine / blood
  • Dogs
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use*
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / therapeutic use*
  • Infusions, Intra-Arterial
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Octreotide / administration & dosage
  • Octreotide / therapeutic use*
  • Pancreas / drug effects*
  • Pancreas / pathology
  • Pancreatitis / drug therapy*
  • Pancreatitis / pathology
  • Thromboxane B2 / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antimetabolites
  • Gastrointestinal Agents
  • Tumor Necrosis Factor-alpha
  • Thromboxane B2
  • Creatinine
  • Amylases
  • Octreotide
  • Fluorouracil