Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice

Understanding the tissue changes and molecular mechanisms of preclinical models is essential for creating an optimal experimental design for credible translation into clinics. In our study, a chlorhexidine (CHX)-induced mouse model of peritoneal fibrosis was used to analyze histological and molecula...

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Main Authors: Neža Brezovec, Nika Kojc, Andreja Erman, Matjaž Hladnik, Jošt Stergar, Matija Milanič, Matija Tomšič, Saša Čučnik, Snežna Sodin-Šemrl, Martina Perše, Katja Lakota
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/11/2726
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author Neža Brezovec
Nika Kojc
Andreja Erman
Matjaž Hladnik
Jošt Stergar
Matija Milanič
Matija Tomšič
Saša Čučnik
Snežna Sodin-Šemrl
Martina Perše
Katja Lakota
author_facet Neža Brezovec
Nika Kojc
Andreja Erman
Matjaž Hladnik
Jošt Stergar
Matija Milanič
Matija Tomšič
Saša Čučnik
Snežna Sodin-Šemrl
Martina Perše
Katja Lakota
author_sort Neža Brezovec
collection DOAJ
description Understanding the tissue changes and molecular mechanisms of preclinical models is essential for creating an optimal experimental design for credible translation into clinics. In our study, a chlorhexidine (CHX)-induced mouse model of peritoneal fibrosis was used to analyze histological and molecular/cellular alterations induced by 1 and 3 weeks of intraperitoneal CHX application. CHX treatment for 1 week already caused injury, degradation, and loss of mesothelial cells, resulting in local inflammation, with the most severe structural changes occurring in the peritoneum around the ventral parts of the abdominal wall. The local inflammatory response in the abdominal wall showed no prominent differences between 1 and 3 weeks. We observed an increase in polymorphonuclear cells in the blood but no evidence of systemic inflammation as measured by serum levels of serum amyloid A and interleukin-6. CHX-induced fibrosis in the abdominal wall was more pronounced after 3 weeks, but the gene expression of fibrotic markers did not change over time. Complement system molecules were strongly expressed in the abdominal wall of CHX-treated mice. To conclude, both histological and molecular changes were already present in week 1, allowing examination at the onset of fibrosis. This is crucial information for refining further experiments and limiting the amount of unnecessary animal suffering.
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spelling doaj.art-4f0f2d788e074e7a9163d49fb56e34412023-11-24T03:49:42ZengMDPI AGBiomedicines2227-90592022-10-011011272610.3390/biomedicines10112726Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in MiceNeža Brezovec0Nika Kojc1Andreja Erman2Matjaž Hladnik3Jošt Stergar4Matija Milanič5Matija Tomšič6Saša Čučnik7Snežna Sodin-Šemrl8Martina Perše9Katja Lakota10Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaInstitute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaFaculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, 6000 Koper, SloveniaReactor Physics Department, Jožef Stefan Institute, 1000 Ljubljana, SloveniaReactor Physics Department, Jožef Stefan Institute, 1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaDepartment of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaUnderstanding the tissue changes and molecular mechanisms of preclinical models is essential for creating an optimal experimental design for credible translation into clinics. In our study, a chlorhexidine (CHX)-induced mouse model of peritoneal fibrosis was used to analyze histological and molecular/cellular alterations induced by 1 and 3 weeks of intraperitoneal CHX application. CHX treatment for 1 week already caused injury, degradation, and loss of mesothelial cells, resulting in local inflammation, with the most severe structural changes occurring in the peritoneum around the ventral parts of the abdominal wall. The local inflammatory response in the abdominal wall showed no prominent differences between 1 and 3 weeks. We observed an increase in polymorphonuclear cells in the blood but no evidence of systemic inflammation as measured by serum levels of serum amyloid A and interleukin-6. CHX-induced fibrosis in the abdominal wall was more pronounced after 3 weeks, but the gene expression of fibrotic markers did not change over time. Complement system molecules were strongly expressed in the abdominal wall of CHX-treated mice. To conclude, both histological and molecular changes were already present in week 1, allowing examination at the onset of fibrosis. This is crucial information for refining further experiments and limiting the amount of unnecessary animal suffering.https://www.mdpi.com/2227-9059/10/11/2726chlorhexidine gluconateperitoneal fibrosismouse modelinflammationcomplement
spellingShingle Neža Brezovec
Nika Kojc
Andreja Erman
Matjaž Hladnik
Jošt Stergar
Matija Milanič
Matija Tomšič
Saša Čučnik
Snežna Sodin-Šemrl
Martina Perše
Katja Lakota
Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice
Biomedicines
chlorhexidine gluconate
peritoneal fibrosis
mouse model
inflammation
complement
title Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice
title_full Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice
title_fullStr Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice
title_full_unstemmed Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice
title_short Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice
title_sort molecular and cellular markers in chlorhexidine induced peritoneal fibrosis in mice
topic chlorhexidine gluconate
peritoneal fibrosis
mouse model
inflammation
complement
url https://www.mdpi.com/2227-9059/10/11/2726
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