Cargando…
Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats
We have previously demonstrated that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) protects the liver via downregulation of hepatic matrix metalloproteinases (MMPs) after ischemia/reperfusion (I/R), which can lead to multiorgan dysfunction. The present study investigated the capacity...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145209/ https://www.ncbi.nlm.nih.gov/pubmed/35631351 http://dx.doi.org/10.3390/ph15050524 |
_version_ | 1784716235209965568 |
---|---|
author | Palladini, Giuseppina Cagna, Marta Di Pasqua, Laura Giuseppina Adorini, Luciano Croce, Anna Cleta Perlini, Stefano Ferrigno, Andrea Berardo, Clarissa Vairetti, Mariapia |
author_facet | Palladini, Giuseppina Cagna, Marta Di Pasqua, Laura Giuseppina Adorini, Luciano Croce, Anna Cleta Perlini, Stefano Ferrigno, Andrea Berardo, Clarissa Vairetti, Mariapia |
author_sort | Palladini, Giuseppina |
collection | PubMed |
description | We have previously demonstrated that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) protects the liver via downregulation of hepatic matrix metalloproteinases (MMPs) after ischemia/reperfusion (I/R), which can lead to multiorgan dysfunction. The present study investigated the capacity of OCA to modulate MMPs in distant organs such as the kidney. Male Wistar rats were dosed orally with 10 mg/kg/day of OCA (5 days) and were subjected to 60-min partial hepatic ischemia. After 120-min reperfusion, kidney biopsies (cortex and medulla) and blood samples were collected. Serum creatinine, kidney MMP-2, and MMP-9-dimer, tissue inhibitors of MMPs (TIMP-1, TIMP-2), RECK, TNF-alpha, and IL-6 were monitored. MMP-9-dimer activity in the kidney cortex and medulla increased after hepatic I/R and a reduction was detected in OCA-treated I/R rats. Although not significantly, MMP-2 activity decreased in the cortex of OCA-treated I/R rats. TIMPs and RECK levels showed no significant differences among all groups considered. Serum creatinine increased after I/R and a reduction was detected in OCA-treated I/R rats. The same trend occurred for tissue TNF-alpha and IL-6. Although the underlying mechanisms need further investigation, this is the first study showing, in the kidney, beneficial effects of OCA by reducing TNF-alpha-mediated expression of MMPs after liver I/R. |
format | Online Article Text |
id | pubmed-9145209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91452092022-05-29 Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats Palladini, Giuseppina Cagna, Marta Di Pasqua, Laura Giuseppina Adorini, Luciano Croce, Anna Cleta Perlini, Stefano Ferrigno, Andrea Berardo, Clarissa Vairetti, Mariapia Pharmaceuticals (Basel) Article We have previously demonstrated that the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) protects the liver via downregulation of hepatic matrix metalloproteinases (MMPs) after ischemia/reperfusion (I/R), which can lead to multiorgan dysfunction. The present study investigated the capacity of OCA to modulate MMPs in distant organs such as the kidney. Male Wistar rats were dosed orally with 10 mg/kg/day of OCA (5 days) and were subjected to 60-min partial hepatic ischemia. After 120-min reperfusion, kidney biopsies (cortex and medulla) and blood samples were collected. Serum creatinine, kidney MMP-2, and MMP-9-dimer, tissue inhibitors of MMPs (TIMP-1, TIMP-2), RECK, TNF-alpha, and IL-6 were monitored. MMP-9-dimer activity in the kidney cortex and medulla increased after hepatic I/R and a reduction was detected in OCA-treated I/R rats. Although not significantly, MMP-2 activity decreased in the cortex of OCA-treated I/R rats. TIMPs and RECK levels showed no significant differences among all groups considered. Serum creatinine increased after I/R and a reduction was detected in OCA-treated I/R rats. The same trend occurred for tissue TNF-alpha and IL-6. Although the underlying mechanisms need further investigation, this is the first study showing, in the kidney, beneficial effects of OCA by reducing TNF-alpha-mediated expression of MMPs after liver I/R. MDPI 2022-04-24 /pmc/articles/PMC9145209/ /pubmed/35631351 http://dx.doi.org/10.3390/ph15050524 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Palladini, Giuseppina Cagna, Marta Di Pasqua, Laura Giuseppina Adorini, Luciano Croce, Anna Cleta Perlini, Stefano Ferrigno, Andrea Berardo, Clarissa Vairetti, Mariapia Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats |
title | Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats |
title_full | Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats |
title_fullStr | Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats |
title_full_unstemmed | Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats |
title_short | Obeticholic Acid Reduces Kidney Matrix Metalloproteinase Activation Following Partial Hepatic Ischemia/Reperfusion Injury in Rats |
title_sort | obeticholic acid reduces kidney matrix metalloproteinase activation following partial hepatic ischemia/reperfusion injury in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145209/ https://www.ncbi.nlm.nih.gov/pubmed/35631351 http://dx.doi.org/10.3390/ph15050524 |
work_keys_str_mv | AT palladinigiuseppina obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT cagnamarta obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT dipasqualauragiuseppina obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT adoriniluciano obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT croceannacleta obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT perlinistefano obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT ferrignoandrea obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT berardoclarissa obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats AT vairettimariapia obeticholicacidreduceskidneymatrixmetalloproteinaseactivationfollowingpartialhepaticischemiareperfusioninjuryinrats |