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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2018-08-01
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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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