Effects of diclofenac sodium and octreotide on treatment of caerulein-induced acute pancreatitis in mice

Abstract

Background: Research continues to develop novel therapeutic modalities that particularly focus on the pathogenesis of acute pancreatitis. This study aimed to assess the effects of diclofenac sodium and octreotide, alone or in combination, on pancreatic enzymes, pancreatic myeloperoxidase activity, histopathology and apoptosis of pancreas cells, using a model of experimentally induced acute pancreatitis.

Objectives: We aimed to demonstrate effects of diclofenac sodium, octreotide and their combined use on pancreatic enzymes, activity of pancreatic myeloperoxidase (MPO) activity, histopathology and apoptosis of pancreas on treatment of caerulin-induced experimental acute pancreatitis.

Materials and methods: Caerulin-induced acute pancreatitis model was created using a total of 58 male BALB-C mice of 25 gr in seven groups. Serum amylase, lipase levels and pancreatic myeloperoxidase activity were examined as well as apoptotic values in pancreatic acinar cells through TUNNEL method. Histopathology of pancreas was evaluated for presence of edema, hemorrhage, parenchymal necrosis, fat necrosis, leukocyte infiltration, and fibrosis.

Results: In the diclofenac sodium group, apoptotic values in the pancreatic acinar cells were found to be statistically lower than in the acute pancreatitis group in terms of parenchymal necrosis and hemorrhage scores (P = 0.007, P = 0.002, and P = 0.052, respectively). No statistically significant differences were found in serum level of amylase, lipase, pancreatic myeloperoxidase activity and the other histopathological scores (P > 0.05).

Conclusion: Diclofenac sodium, a cost-effective agent with a favorable side-effect profile, may represent a novel therapeutic agent for the treatment of acute pancreatitis. Findings of this study suggest a better efficacy for diclofenac sodium monotherapy as compared to octreotide alone or octreotide/diclofenac combination.

Keywords: Diclofenac sodium; experimental acute pancreatitis; octreotide.

Figure 1

A. Plasma levels of amylase (U/L). Effects of octreotide and diclofenac sodium on acute-pancreatitis induced hyperamylasemia. Tag 1: Represents baseline amylase levels for each group; Tag 2: Represents post-treatment amylase levels. *P < 0.05 for comparison with the control group; ┼P < 0.05 for comparison with acute pancreatitis group. B. Plasma levels of lipase (IU/L). Effects of octreotide and diclofenac sodium on acute-pancreatitis induced hyperamylasemia. Tag 1: Represents baseline lipase levels for each group; Tag 2: Represents post-treatment lipase levels. *P < 0.05 for comparison with the control group; ┼P < 0.05 for comparison with acute pancreatitis group.

Figure 2

A. The mean of apoptosis counts in the groups. The mean apoptotic value in the Group 2 was significantly higher than in the Group 6 between treatment groups (P = 0.007). *P < 0.05. B. Immunohistochemically apopitosis. a: Group 2, b: Group 6. Nucleus of apopitotic positive cells appear brown in color. (TUNNEL method ×200).

Figure 3

A. Distribution of histopathological scores for edema, hemorrhage and parenchymal necrosis in the pancreatic tissue among the groups. B. Distribution of histopathological scores for fat necrosis, leukocyte infiltration and fibrosis in the pancreatic tissue among the groups.

Figure 4

Group 6 (1), Group 5 (2), Group 7 (3) groups of hemorrhage and inflammation (A), edema (B), parenchymal necrosis (C-yellow arrows). (A. Hematoxylin & Eosin ×100, Bar = 100 µm; B, C. Hematoxylin & Eosin ×40, Bar = 40 µm).

Figure 5

The mean of histopathological scores. It was observed that edema was statistically significant higher in the Group 5 compared to Group 2 (P = 0.049) Edema scores were significantly lower in the diclofenac group when compared to the octreotide group (P = 0.025). When the Group 2 was compared to Group 6 in terms of presence of hemorrhage, it was found that hemorrhage was significantly lower in the Groups 6 (P = 0.052). When the Group 2 was compared to the other groups, parenchymal necrosis was significantly lower in the Groups 6 (P = 0.002) *P < 0.05.