Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model

Background Intra-abdominal adhesions develop after nearly every abdominal surgery, commonly causing female infertility, chronic pelvic pain, and small bowel obstruction. Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The aim of this study was to...

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Main Authors: Ya-Lin Yang, Meng-Tse Gabriel Lee, Chien-Chang Lee, Pei-I Su, Chien-Yu Chi, Cheng-Heng Liu, Meng-Che Wu, Zui-Shen Yen, Shyr-Chyr Chen
Format: Article
Language:English
Published: PeerJ Inc. 2018-08-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/5434.pdf
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author Ya-Lin Yang
Meng-Tse Gabriel Lee
Chien-Chang Lee
Pei-I Su
Chien-Yu Chi
Cheng-Heng Liu
Meng-Che Wu
Zui-Shen Yen
Shyr-Chyr Chen
author_facet Ya-Lin Yang
Meng-Tse Gabriel Lee
Chien-Chang Lee
Pei-I Su
Chien-Yu Chi
Cheng-Heng Liu
Meng-Che Wu
Zui-Shen Yen
Shyr-Chyr Chen
author_sort Ya-Lin Yang
collection DOAJ
description Background Intra-abdominal adhesions develop after nearly every abdominal surgery, commonly causing female infertility, chronic pelvic pain, and small bowel obstruction. Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The aim of this study was to investigate whether PTX can reduce post-operative intra-abdominal adhesion formation via collagen deposition, tissue plasminogen activator (tPA) level, inflammation, angiogenesis, and fibrosis. Methods Seventy male BALB/c mice were randomized into one of three groups: (1) sham group without peritoneal adhesion model; (2) peritoneal adhesion model (PA group); (3) peritoneal adhesion model with PTX (100 mg/kg/day i.p.) administration was started on preoperative day 2 and continued daily (PA + PTX group). On postoperative day 3 and day 7, adhesions were assessed using the Lauder scoring system. Parietal peritoneum was obtained for histological evaluation with hematoxylin and eosin (HE) and picrosirius red staining. Fibrinolysis was analyzed by tPA protein levels in the peritoneum by ELISA. Immunohistological analysis was also conducted using markers for angiogenesis (ki67+/CD31+), inflammation (F4/80+) and fibrosis (FSP-1+ and α-SMA+). All the comparisons were made by comparing the PA group with the PTX treated PA group, and p < 0.05 was considered statistically significant. Results Intra-abdominal adhesions were markedly reduced by PTX treatment. Compared with the PA group, PTX treatment had lower adhesion scores than the PA group on both day 3 and day 7 (p < 0.05). Histological evaluations found that PTX treatment reduced collagen deposition and adhesion thickening. ELISA analysis showed that PTX treatment significantly increased the level of tPA in the peritoneum. In addition, in the immunohistological analysis, PTX treatment was found to significantly decrease the number of ki67+/CD31+ cells at the site of adhesion. Finally, we also observed that in the PTX treated group, there was a reduction in the expression of F4/80+, FSP-1+, and α-SMA+ cells at the site of adhesion. Conclusion PTX may decrease intra-abdominal adhesion formation via increasing peritoneal fibrinolytic activity, suppressing angiogenesis, decreasing collagen synthesis, and reducing peritoneal fibrosis. Our findings suggest that PTX can be used to decrease post-operative intra-abdominal adhesion formation.
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spelling doaj.art-3d68678895794fa58606ec5542ca57ee2023-12-03T10:02:44ZengPeerJ Inc.PeerJ2167-83592018-08-016e543410.7717/peerj.5434Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal modelYa-Lin Yang0Meng-Tse Gabriel Lee1Chien-Chang Lee2Pei-I Su3Chien-Yu Chi4Cheng-Heng Liu5Meng-Che Wu6Zui-Shen Yen7Shyr-Chyr Chen8Department of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanDepartment of Emergency Medicine, National Taiwan University Hospital and College of Medicine, Taipei, TaiwanBackground Intra-abdominal adhesions develop after nearly every abdominal surgery, commonly causing female infertility, chronic pelvic pain, and small bowel obstruction. Pentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The aim of this study was to investigate whether PTX can reduce post-operative intra-abdominal adhesion formation via collagen deposition, tissue plasminogen activator (tPA) level, inflammation, angiogenesis, and fibrosis. Methods Seventy male BALB/c mice were randomized into one of three groups: (1) sham group without peritoneal adhesion model; (2) peritoneal adhesion model (PA group); (3) peritoneal adhesion model with PTX (100 mg/kg/day i.p.) administration was started on preoperative day 2 and continued daily (PA + PTX group). On postoperative day 3 and day 7, adhesions were assessed using the Lauder scoring system. Parietal peritoneum was obtained for histological evaluation with hematoxylin and eosin (HE) and picrosirius red staining. Fibrinolysis was analyzed by tPA protein levels in the peritoneum by ELISA. Immunohistological analysis was also conducted using markers for angiogenesis (ki67+/CD31+), inflammation (F4/80+) and fibrosis (FSP-1+ and α-SMA+). All the comparisons were made by comparing the PA group with the PTX treated PA group, and p < 0.05 was considered statistically significant. Results Intra-abdominal adhesions were markedly reduced by PTX treatment. Compared with the PA group, PTX treatment had lower adhesion scores than the PA group on both day 3 and day 7 (p < 0.05). Histological evaluations found that PTX treatment reduced collagen deposition and adhesion thickening. ELISA analysis showed that PTX treatment significantly increased the level of tPA in the peritoneum. In addition, in the immunohistological analysis, PTX treatment was found to significantly decrease the number of ki67+/CD31+ cells at the site of adhesion. Finally, we also observed that in the PTX treated group, there was a reduction in the expression of F4/80+, FSP-1+, and α-SMA+ cells at the site of adhesion. Conclusion PTX may decrease intra-abdominal adhesion formation via increasing peritoneal fibrinolytic activity, suppressing angiogenesis, decreasing collagen synthesis, and reducing peritoneal fibrosis. Our findings suggest that PTX can be used to decrease post-operative intra-abdominal adhesion formation.https://peerj.com/articles/5434.pdfAngiogenesisTissue plasminogen activator levelPentoxifyllineInflammationFibrosisIntra-abdominal adhesion formation
spellingShingle Ya-Lin Yang
Meng-Tse Gabriel Lee
Chien-Chang Lee
Pei-I Su
Chien-Yu Chi
Cheng-Heng Liu
Meng-Che Wu
Zui-Shen Yen
Shyr-Chyr Chen
Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model
PeerJ
Angiogenesis
Tissue plasminogen activator level
Pentoxifylline
Inflammation
Fibrosis
Intra-abdominal adhesion formation
title Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model
title_full Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model
title_fullStr Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model
title_full_unstemmed Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model
title_short Pentoxifylline decreases post-operative intra-abdominal adhesion formation in an animal model
title_sort pentoxifylline decreases post operative intra abdominal adhesion formation in an animal model
topic Angiogenesis
Tissue plasminogen activator level
Pentoxifylline
Inflammation
Fibrosis
Intra-abdominal adhesion formation
url https://peerj.com/articles/5434.pdf
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