Effects of pioglitazone and metformin on abdominal adhesion formation in an experimental model

Abstract

Background: This study evaluated the use of metformin or pioglitazone in preventing or reducing the development of post-operative intra-abdominal adhesion (PIAA) by employing histopathological, immunohistochemical, and biochemical analyses in an experimental adhesion model.

Methods: Fifty Wistar-Albino rats were divided into five groups: Group I (Control), Group II (Sham Treatment), Group III (Hy-aluronic Acid), Group IV (Metformin), and Group V (Pioglitazone). Adhesions were induced in the experimental groups, except for the sham group, using the scraping method. After 10 days, rats were euthanized for evaluation. Macroscopic adhesion degrees were assessed using Nair's scoring system. Immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods were utilized to assess serum, peritoneal lavage, and intestinal tissue samples. Fructosamine, interleukin-6 (IL-6), transforming growth factor-beta (TGF-β), and fibronectin levels were measured in serum and peritoneal lavage samples.

Results: The groups exhibited similar Nair scores and Type I or Type III Collagen staining scores (all, p>0.05). Pioglitazone significantly reduced serum IL-6 and TGF-β levels compared to controls (p=0.002 and p=0.008, respectively). Both metformin and pioglitazone groups showed elevated IL-6 in peritoneal lavage relative to controls, while fibronectin levels in the lavage were lower in pioglitazone-treated rats compared to the sham group (all, p<0.005).

Conclusion: Pioglitazone, but not metformin, demonstrated a positive biochemical impact on preventing PIAA formation in an experimental rat model, although histological impacts were not observed. Further experimental studies employing different dose/duration regimens of pioglitazone are needed to enhance our understanding of its effect on PIAA formation.

Figure 1

Model demonstrating direct mechanical damage to the bowel wall via gauze scraping and ischemic damage through vascular clamping.

Figure 2

Inflammatory cell infiltration and micro abscess formation, H&E stained (400x magnification).

Figure 3

Over 66% area stained for collagen type I and III, IHC staining at 200x magnification.

Figure 4

Serum fructosamine levels across different study groups.

Figure 5

Serum IL-6 levels analyzed across various groups.

Figure 6

Serum fibronectin levels categorized by group.

Figure 7

Serum TGF-β levels across various groups.

Figure 8

Peritoneal lavage IL-6 levels measured across groups.

Figure 9

Peritoneal lavage fibronectin levels across different groups.

Figure 10

TGF-β levels in peritoneal lavage analyzed by group.