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Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis
Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodyn...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836491/ https://www.ncbi.nlm.nih.gov/pubmed/35160088 http://dx.doi.org/10.3390/jcm11030636 |
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author | Donadei, Chiara Angeletti, Andrea Cappuccilli, Maria Conti, Massimiliano Conte, Diletta Zappulo, Fulvia De Giovanni, Alessio Malvi, Deborah Aldini, Rita Roda, Aldo La Manna, Gaetano |
author_facet | Donadei, Chiara Angeletti, Andrea Cappuccilli, Maria Conti, Massimiliano Conte, Diletta Zappulo, Fulvia De Giovanni, Alessio Malvi, Deborah Aldini, Rita Roda, Aldo La Manna, Gaetano |
author_sort | Donadei, Chiara |
collection | PubMed |
description | Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl(4)) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl(4) administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI. |
format | Online Article Text |
id | pubmed-8836491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88364912022-02-12 Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis Donadei, Chiara Angeletti, Andrea Cappuccilli, Maria Conti, Massimiliano Conte, Diletta Zappulo, Fulvia De Giovanni, Alessio Malvi, Deborah Aldini, Rita Roda, Aldo La Manna, Gaetano J Clin Med Article Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl(4)) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl(4) administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI. MDPI 2022-01-27 /pmc/articles/PMC8836491/ /pubmed/35160088 http://dx.doi.org/10.3390/jcm11030636 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 Donadei, Chiara Angeletti, Andrea Cappuccilli, Maria Conti, Massimiliano Conte, Diletta Zappulo, Fulvia De Giovanni, Alessio Malvi, Deborah Aldini, Rita Roda, Aldo La Manna, Gaetano Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis |
title | Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis |
title_full | Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis |
title_fullStr | Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis |
title_full_unstemmed | Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis |
title_short | Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis |
title_sort | adaptive mechanisms of renal bile acid transporters in a rat model of carbon tetrachloride-induced liver cirrhosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836491/ https://www.ncbi.nlm.nih.gov/pubmed/35160088 http://dx.doi.org/10.3390/jcm11030636 |
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