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Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response

Ischemia-reperfusion (IR) is a common risk factor that causes acute kidney injury (AKI). AKI is associated with dysfunction of other organs also known as distant organ injury. The liver function is often compromised in patients with AKI and in animal models. However, the underlying mechanisms are no...

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Autores principales: Shang, Yue, Madduma Hewage, Susara, Wijerathne, Charith U. B., Siow, Yaw L., Isaak, Cara K., O, Karmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280447/
https://www.ncbi.nlm.nih.gov/pubmed/32582723
http://dx.doi.org/10.3389/fmed.2020.00201
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author Shang, Yue
Madduma Hewage, Susara
Wijerathne, Charith U. B.
Siow, Yaw L.
Isaak, Cara K.
O, Karmin
author_facet Shang, Yue
Madduma Hewage, Susara
Wijerathne, Charith U. B.
Siow, Yaw L.
Isaak, Cara K.
O, Karmin
author_sort Shang, Yue
collection PubMed
description Ischemia-reperfusion (IR) is a common risk factor that causes acute kidney injury (AKI). AKI is associated with dysfunction of other organs also known as distant organ injury. The liver function is often compromised in patients with AKI and in animal models. However, the underlying mechanisms are not fully understood. Inflammatory response plays an important role in IR-induced tissue injury. Although increased proinflammatory cytokines have been detected in the kidney and the distant organs after renal IR, their original sources remain uncertain. In the present study, we investigated the acute effect of renal IR on hepatic inflammatory cytokine expression and the mechanism involved. Sprague-Dawley rats that were subjected to renal IR (ischemia for 45 min followed by reperfusion for 1 h or 6 h) had increased plasma levels of creatinine, urea, and transaminases, indicating kidney and liver injuries. There was a significant increase in the expression of proinflammatory cytokine mRNA (MCP-1, TNF-α, IL-6) in the kidney and liver in rats with renal IR. This was accompanied by a significant increase in proinflammatory cytokine protein levels in the plasma, kidney, and liver. Activation of a nuclear transcription factor kappa B (NF-κB) was detected in the liver after renal IR. The inflammatory foci and an increased myeloperoxidase (MPO) activity were detected in the liver after renal IR, indicating hepatic inflammatory response and leukocyte infiltration. These results suggest that renal IR can directly activate NF-κB and induce acute production of proinflammatory cytokines in the liver. Renal IR-induced hepatic inflammatory response may contribute to impaired liver function and systemic inflammation.
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spelling pubmed-72804472020-06-23 Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response Shang, Yue Madduma Hewage, Susara Wijerathne, Charith U. B. Siow, Yaw L. Isaak, Cara K. O, Karmin Front Med (Lausanne) Medicine Ischemia-reperfusion (IR) is a common risk factor that causes acute kidney injury (AKI). AKI is associated with dysfunction of other organs also known as distant organ injury. The liver function is often compromised in patients with AKI and in animal models. However, the underlying mechanisms are not fully understood. Inflammatory response plays an important role in IR-induced tissue injury. Although increased proinflammatory cytokines have been detected in the kidney and the distant organs after renal IR, their original sources remain uncertain. In the present study, we investigated the acute effect of renal IR on hepatic inflammatory cytokine expression and the mechanism involved. Sprague-Dawley rats that were subjected to renal IR (ischemia for 45 min followed by reperfusion for 1 h or 6 h) had increased plasma levels of creatinine, urea, and transaminases, indicating kidney and liver injuries. There was a significant increase in the expression of proinflammatory cytokine mRNA (MCP-1, TNF-α, IL-6) in the kidney and liver in rats with renal IR. This was accompanied by a significant increase in proinflammatory cytokine protein levels in the plasma, kidney, and liver. Activation of a nuclear transcription factor kappa B (NF-κB) was detected in the liver after renal IR. The inflammatory foci and an increased myeloperoxidase (MPO) activity were detected in the liver after renal IR, indicating hepatic inflammatory response and leukocyte infiltration. These results suggest that renal IR can directly activate NF-κB and induce acute production of proinflammatory cytokines in the liver. Renal IR-induced hepatic inflammatory response may contribute to impaired liver function and systemic inflammation. Frontiers Media S.A. 2020-06-02 /pmc/articles/PMC7280447/ /pubmed/32582723 http://dx.doi.org/10.3389/fmed.2020.00201 Text en Copyright © 2020 Shang, Madduma Hewage, Wijerathne, Siow, Isaak and O. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Shang, Yue
Madduma Hewage, Susara
Wijerathne, Charith U. B.
Siow, Yaw L.
Isaak, Cara K.
O, Karmin
Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response
title Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response
title_full Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response
title_fullStr Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response
title_full_unstemmed Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response
title_short Kidney Ischemia-Reperfusion Elicits Acute Liver Injury and Inflammatory Response
title_sort kidney ischemia-reperfusion elicits acute liver injury and inflammatory response
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280447/
https://www.ncbi.nlm.nih.gov/pubmed/32582723
http://dx.doi.org/10.3389/fmed.2020.00201
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